The main game begins with Tycho receiving a phone call which is described as 10 minutes of silence, prompting Tycho and Gabe to go to the Arcadia boardwalk where they had previously defeated the mime god and members of his cult. Teaming up with Anne-Claire, they fight past the cultists, and eventually face off against a crabomancer, then, upon defeating it, recover pins which bestow classes on whomever wears one (similar to the job system in early Final Fantasy games). They return to their office, only to find that Dr. Blood has orchestrated the theft of the Necrowombicon. Anne-Claire returns home, Tycho and Gabe team up with Jim, a former colleague who lost his body in a work-related incident, reducing him to a skull floating in a jar of green liquid. Jim is unable to speak, but can follow Tycho and Gabe, as well as participate in combat. Following leads, they arrive at the museum of contemporary and ancient works, where Tycho is reunited with Moira, his ex-wife, who joins the party. When asked if they can re-recruit Anne-Claire, Tycho answers she is on vacation with her parents. The party discovers that a painting has been stolen from the museum, the painting being one of four representing the god of doors, Yog-Modaign, a death-god like figure.

Now also investigating the theft of the painting, the party, acting on advice of Dr. Euripides Hark, head for the Hark ancestral home. However, as the Harks are an old family and possess superior arcane know-how to Tycho, Tycho forces the party to use an alternate entrance, a trans-dimensional door accessible only via another dimension. The party returns to the detective agency to pick up a device capable of allowing them to enter this dimension, but it is revealed that, in his ignorance of what the object was (it resembles a stein), Gabe gave it to a local homeless man. The party goes to Hobo alley to recover it, and then head into the other dimension called the Periphery, represented by a stone path leading to multiple gateways, dotted with floating crystals. Tycho explains that the crystals are in fact, coffins, or time capsules, usually containing powerful mages or mythical creatures. Since the other dimension would survive any apocalypse, the contents of the crystal time capsules would inevitably be used to determine the properties of the world to come after the end of ours. The Brahe clan's long project, which Tycho and his family frequently speak of, is to wipe out these time capsules, as everyone would "get it wrong" and recreate the universe poorly.