After leaving Hongyuan, the Sinners wait in an LCCB transporter truck for a planned meeting with Saude, Vergilius, and Pilot. As they start to worry about Saude's uncharacteristic tardiness, she runs in, heavily wounded, with the news that the Limbus Company headquarters is being invaded, and that she and the others were attacked by members of the Thumb. As Saude gets to work on forming a portal leading to the Limbus Company HQ, they receive a transmission by one of the assailants at the HQ, who directly addresses Ryōshū, calling her his "darling daughter" and asking her to come home. Ryōshū understands that her turn has come, and warns Dante that the "Spiders" have come to spin their web. Soon after, Vergilius returns, locked in combat with two members of the Thumb, Lucio and Valencina, burst into the truck, who are holding Charon hostage.

As Vergilius, unsettled and handicapped by the threat to Charon's life, clashes blades with Valencina, the woman is identified by Ryōshū as "the Thumb Nursefather", one of the members of the Five Fingers who had raised her, belonging to an organization called the House of Spiders. The two have a heated exchange, in which Valencina talks down to Ryōshū, and tells her that she will soon leave the company to return home. As the portal leading to the HQ opens, Valencina tells her to go ahead, as the other Nursefathers are waiting for her; while Vergilius remains behind with Valencina, the Sinners pass through the portal.

The Sinners find the headquarters in total disarray, with countless researchers dead, stabbed with peculiar spiral-shaped weapons. Among them, the Sinners find Alyssa, who lays in critical condition, but still manages to speak. Alyssa recalls the sudden circumstances of the attack and of the weapon that stabbed her, and Ryōshū understands that the only way to save her would be to "unlock" the spiral with a code, which she previously knew, but no longer can recall. As Dante starts to get a glimpse of her memories, they find them to be heavily censored and ragged, and Ryōshū herself explains that her memory is in tatters. The Sinners then decide to keep moving forward, and return for Alyssa.

After fighting through a number of escaped Abnormalities and Ring automatons, they eventually run into Hohenheim, Marton, Moses, Ezra, and the LCD's newly-hired Aeng-du barricaded in the HQ's broadcast sector. The two groups exchange information, and the Sinners learn that the LCE had been running an experiment on the retrieved Golden Boughs, having managed to graft them together. It becomes clear that the attack started in an attempt by the House of Spiders to take the grafted Bough.

Together, they agree that the Sinners would secure the Golden Boughs, the LCD would fight off roaming monsters, and the LCE would restore power to the facility. Unfortunately, the shifting walls of the laboratory end up grouping them into unexpected teams: Dante with Yi Sang, Gregor, Meursault, and Ryōshū, then Moses with Ezra, Aeng-du, Ishmael, Rodya, Outis, and Hong Lu, and lastly Hohenheim with Marton, Faust, Heathcliff, Sinclair, and Don Quixote. In the end, Dante's team agree to go after the Boughs, while Moses' team neutralized hostiles and Hohenheim's restored power.

In the meantime, Dante's group witness a wave of LCA agents arriving to the facility to deal with the chaos, only to be intercepted by the Nursefather of the Index, Rien, who effortlessly dispatches them. With no choice but to carry on, the group makes their way to the room housing the Golden Boughs, only to run into the Nursefather of the Pinky, the Dihui Star, her apprentice Ren, and the Ring apprentice Albina. While Ren and Albina engage in battle with the four Sinners, the Pinky Nursefather leaves with the Boughs. During the battle, the two apprentices turn on each other, which allows the Sinners to run away, chasing after the Dihui Star. As they make their way forward, Ryōshū reveals that her tattered memories are a side effect of unsheathing her blade, that she had a daughter whom she had left hidden in a Time Vault at the House of Spiders, and that she'd signed her contract with the LCB to be able to return to her and free her.

On their way, the group runs into two new hires named Ravi and Sora, who'd survived the attack but had been trapped beneath fallen rubble. Sora offers to guide their group to the elevator, and the two join the group. Having reached it and come face to face with the Pinky Nursefather, Sora reveals herself to be the apprentice to the Index Nursefather, and her true allegiance to lay with the House. Sora manifests her Effloresced E.G.O and strikes to kill Dante, and the Sinner four members of the LCB engage in a difficult battle with Sora. They're saved by the surprise appearance of Vespa, who makes quick work of Sora before departing for his other allies, leaving the Sinners alone with the Dihui Star, Shiomi Yoru. In order to stand a chance against the Nursefather, Dante attempts to unlock a new Sapling of Light ability: they manage to summon the Identities of Sinners who were not present, with the consequence of causing the real Sinners to fall unconscious where they were, leaving the LCD and LCE members to fend for themselves.

Meanwhile, Moses' group managed to restore the security cameras: through them, they see the Middle Nursefather Matthias storming through the facility, and they're surprised to find his daughter, Kira, has made her way to their hiding spot. As the two Middle members reunite, the group tries to escape, freeing various Abnormalities and Distortions in an attempt to hold them off. Matthias cuts through it all, and the group ends up having to face him in battle. However, the Sinners summoned through Dante's Sapling of Light ability suddenly pass out, leaving Ezra, Moses and Aeng-du to face him alone. Matthias overwhelms them in combat, with Aeng-du losing first her sword, then both of her arms. Before the encounter turns fatal, however, Vespa arrives to their aid, although before he can properly face the Nursefather, Matthias hears word that the other members of the House have achieved their goal, and he and Kira retreat.

On the other side of the facility, Hohenheim and Marton struggle against Callisto, the Nursefather of the Ring. Although the Sinners had agreed to keep the Nursefather busy while they restored the facility's power grid, with the Sinners passing out they remain alone and unable to match him in combat. As the Nursefather closes in, Marton goes on ahead to protect Hohenheim, setting his E.G.O Attunement to fatal levels in order to distract the Nursefather and give Hohenheim enough time to restart the power grid. Like Matthias, Callisto retreats soon after, upon receiving news of the Bough retrieval. Back in the LCCB transporter truck, Valencina and Lucio do the same.

In the meantime, at the elevators where Dante had summoned the rest of the LCB, the Sinners face off against the Dihui Star, but are slowly overwhelmed. During the battle, Ryōshū comments on how she's glad she'd severed the Nursefather's tongue with her sword, as every wound made with that blade will always reopen in its presence; she is then shocked to find the Dihui Star can still speak, and reveals that the Nursefather had been aware of Ryōshū's plan to save her daughter, which had involved locking her in a small safe, a Time Vault hidden somewhere in the House of Spiders. After defeating the Sinners in battle, the Dihui Star contacts the other Nursefathers, before making her escape. The Index Nursefather joins her soon after, retrieving Sora and giving Ryōshū the code to the spiral weapons, and leaving behind the safe where Ryōshū had hidden her child, Araya. Ryōshū desperately tears open the safe, only to find it empty, leading her to pass out from shock.

Some time later, the surviving members of Limbus Company regroup with the intention of raiding the House of Spiders and getting revenge on the Nursefathers through Operation Spider Pyre.

The operation has the Sinners separated into four groups of three, backed by other Limbus Company personnel: Sinclair, Ishmael, and Faust, with Hohenheim and Alyssa facing Ring the Nursefather Callisto and his apprentice Albina; Don Quixote, Hong Lu, and Yi Sang with Moses, Ezra, and Vespa against the Middle Nursefather Matthias and his apprentice Kira; Gregor, Heathcliff, and Rodion with Vergilius against the Thumb Nursefather Valencina and her apprentice Lucio; Ryōshū, Meursault, and Outis with LCA Udjat Vanguard Team 1 led by Jamila against the Index and Pinky Nursefathers Rien and Shiomi Yoru. The groups enter the House of Spiders through the Backdoor, each of them landing in the Finger's corresponding Corridor.

During the confrontation with the Ring, the entire group is overwhelmed, but as Alyssa and Hohenheim are nearly killed by Callisto, Sinclair's Sign awakens, summoning a version of himself from a future where he is a veteran of a Second Smoke War, which was fought between humans and humans who "no longer looked the part", such as prosthetic users and Distortions. This version of Sinclair manages to turn the tide on the battle, and ultimately destroys both Albina and Callisto.

Meanwhile, Moses' group manages to get the upper hand over the Middle. In an attempt to kill Vespa, Matthias uses Kira as a distraction, and bisects her to land an attack that Vespa dodges. While Hong Lu treats Kira's wounds and saves her from the fatal wound, Matthias is finally defeated, dying at the hands of Vespa and Moses.

In the encounter against Thumb the Nursefather Valencina and her apprentice Lucio, Gregor is targeted by Valencina, a Smoke War veteran who had fought against the Old G Corp. As the battle drags on, Lucio, who had sustained heavy wounds in the previous encounter with Vergilius, is unable to keep fighting, leading to Valencina verbally assaulting him with a brutality that shocks the Sinners. In particular, Gregor is reminded of similar words he'd received from Hermann, and he grows more unstable, until Lucio attempts a final attack against him. Under this stress, Gregor becomes unable to control his arm, which extends and pierces Lucio in the chest, ripping out his heart and killing him. While attacked by Valencina in a fit of rage, Gregor further loses control of himself, and begins metamorphosizing into a new form: the fourth decisive weapon of the Old G Corp., The Roach Emperor. In this form, Gregor kills Valencina, and he is ultimately knocked out and brought back to normalcy by the other three.

The last group of Sinners is separated from their companions: Jamila and the Udjat are transported to the Corridor of the Index, where they are effortlessly wiped out by Rien, while the Sinners themselves head into the Corridor of the Pinky, where they encounter the Dihui Star again. During the battle, as she and Ryōshū speak, Dante catches glimpses of Ryōshū's memories. As the Sinners face off against the Pinky Nursefather, they learn of Ryōshū's upbringing in the House of Spiders, and that she had been born of the Dihui Star, whose blood made her the right wielder for her sword, the Relic "Arayashiki"; Araya had instead been produced by the Thumb as another possible candidate to wield the Relic, but was instead taken in by Ryōshū, who raised her as a normal child. While some of the Nursefathers were initially opposed to this, Rien would come to find a use in Araya, seeing her as a "fetter" that could bind Ryōshū to the House.

In her youth, after one of her tutors, Lei Heng, convinced Ryōshū to unsheathe Arayashiki, she would learn that the sword had the side effect of cutting away one of her dearest memories whenever it was wielded unsheathed, and after that incident, Ryōshū would only be made to wield the sword unsheathed upon collective agreement of the Nursefathers. After adopting Araya, Ryōshū understood that having to wield it at the request of the Nursefather meant the sword threatened to steal her memories of her daughter, and decided to find a way to free the two of them from the House of Spiders. Eventually, Ryōshū had Araya hide in the Vault with the intent of keeping her safe until she could come back strong enough to destroy the House, and began cutting her way through the Nursefathers in her escape.

Upon facing the Pinky Nursefather now, Ryōshū remembers the moment she had attacked Shiomi Yoru before leaving, cutting her tongue out as Yoru reminded her she would never be free of the House of Spiders. As Ryōshū strikes the Pinky Nursefather down, piercing through her heart, it was revealed that during their last encounter, Ryōshū had already killed Shiomi Yoru in the very same way, but the memory had been mutilated by the sword, leading her to forgetting about this. The dying Dihui Star reveals that she is actually Araya, who had opened the safe and become "temporally entangled", an event that made her experience numerous decades inside the safe, causing her to grow old and at times "shift" between her young and aged selves. She was found by Rien, who offered her to take the vacant seat of the Pinky Nursefather, as working with the House would allow her to come face to face to Ryōshū again.

Upon realizing the truth, a grieving Ryōshū severs her contract with Dante and begins using Arayashiki in reckless abandon. Rien, Sora and Ren soon appear on the scene, with Rien commenting, rejoiced, that Ryōshū has entered a state of "non-self". When Sora and Ren go forward to face Ryōshū in battle, Arayashiki erases them completely, to the point that Rien and the Sinners, save for Dante, soon forget their names. As Ryōshū becomes nothing more but a vortex of slashes to try and carve herself out from existence, Rien reveals that this current state is the true form of what the House of Spiders sought to create: a perfect wielder of Arayashiki, which becomes something akin to a human Concept Incinerator, for anyone to dump their unwanted secrets in and be forgotten forever.

However, Araya, still holding onto life and now aware Ryōshū had always intended to come back for her, asks for Dante's help in reaching out to her mother: with the help of a new Durante ability, Ira, Dante is able to craft a new chain, which Araya brings to Ryōshū, reaffirming her love. This reinstates Ryōshū's contract and creates a new scabbard for Arayashiki made from Araya's own E.G.O, but at the cost of Araya herself being slashed away. Rien then steps up as the final opponent to prevent Ryōshū from leaving, and Dante, using the incomplete Malkuth and new Ira abilities, summons all the Sinners to face the last Nursefather. With one last swing of Arayashiki, Ryōshū severs herself from the House of Spiders, defeating Rien, but allowing him to escape.

By the end of the operation, but every threat of the House annihilated, the Golden Boughs are found tucked away in Araya's red randoseru. After returning to the LCCB transporter truck, Dante considers how Ryōshū has forgotten everything about Araya, but Faust states that according to the principle of entanglement, as long as half of a connection exists, the other might one day be restored as well, hinting at the possibility that as long as Ryōshū holds onto her scabbard, she might one day find her daughter again.

Somewhere else in the City, a severely injured Rien encounters and fights off multiple Index Proxies, who are pursuing him for his failure to obey a Prescript. As he collapses to the ground, he receives one Prescript, which asks him to recite a certain poem to mimic the death of the Black Silence, but he trails off while doing so, deciding it is too tiring. Instead, he wishes his daughter the best, and kills himself with the only weapon the Prescript allows him to use, a spork.

Elsewhere, Faust conducts a Classical Walpurgisnacht meeting with the Gesellschaft, to request information regarding the security leak that allowed the House of Spiders to make their way to the Limbus Company HQ. After some belittling from the other Fausts, it was revealed that the leak and sabotage was from Dias, the Chief Executive Director of the Company. More mockery reveals that the Sinner Faust was a former administrator to the Gesellschaft, and that while she has been the most fruitful Faust in her search for the Boughs, she will need to collect them, "plant the sapling and harvest an apple from it" to gain a chance to be reinstated.

Meanwhile, the New League of Nine Littérateurs is informed by Nelly of the operation and Limbus Company's counterstrike against the House of Spiders, before Hermann requests Nelly to keep following the group. The members of the New League then prepare to walk into a meeting, where the board of N Corp. will be discussing the organization of a purge against prosthetic users, spearheaded by Jacob and Heinrich Kromer, the "Ones Who Grip", which will allow the New League to go on with their plan for destroying all Mirror Worlds.