Several months after Episode One ended, the Player has rebuilt his/her house (a tent), and Tycho and Gabe have set out to destroy Fruit Fuckers and try to find a lead on Fruit Fucker Prime. While escaping from a swarm of them, they crash a truck into the Player's (partially rebuilt) house, and recruit him/her to help them track down their lead. A trip to Anne-Claire's reveals that they have found the original designer of the Fruit Fuckers: Dr. Jonathan Crazoir, presently incarcerated in the same sanatorium as Tycho's father and grandfather when they succumbed to the insanity inherent to dealing with otherworldy affairs. She also demands they collect various pieces of equipment for one of her experiments: Five bolts of silk thread, preferably spider silk, a golden bolt, a truck or tractor engine, and a molecule of Energite, a highly unstable element. They enter the sanitarium to find Crazoir, who promises to give Tycho, Gabe, and the Player everything related to his research, as well as a "robot monkey card", if they can free him from the madhouse. After wooing the receptionist, they encounter huntsman/sanatorium owner Dr. Wolfington, who has used the millions made from the Brahe family's inevitable descent into madness to hunt down and kill every rare animal in the world. He declares the Player, Tycho, and Gabe all unfit for society after a rigged ink blot test, and has them injected with various chemicals to induce insanity.

The Player fights off the drugs with the help of Twisp and Catsby, and rescues Tycho and Gabe. A guard catches them, and locks down the facility. This seals off Dr. Wolfington's doors with Strengthium, an unbreakable compound. Anne-Claire donates spare parts to fix the doors, but the power difference between her experimental fuse and the security system unseals all doors in the facility, releasing several giant spiders. The trio harvests them for their silk, as per Anne-Claire's request, collects the engine from the truck that Tycho crashed into the Player's house at the beginning of the game, and return to confront Wolfington. After the fight, they forge release papers for Crazoir and read Wolfington's journal. Crazoir is revealed to have been committed as a favor to the mysterious "M", whose address is written down. The now-free Dr. Crazoir gives over his research, which suggests the Fruit Fucker to originally have been a farming tool called "Harvest Buddy", before the designs were stolen by someone as he was abducted by Dr. Wolfington.