CthulhuTech is set on Earth in 2085, during a veritable world war known as the "Aeon War," against aliens and cultists with varying goals. Due to the Aeon War, the political layout of the world has changed greatly. The remainder of the civilized world has joined forces to create the New Earth Government, comprising mainly Western Europe, China, Japan, Australia, and the Americas.

Vast swathes of Asian and European territory have been destroyed by the rapidly expanding Rapine Storm, a cult of crazed psychopaths and cannibals who ravage the land in hordes of armed men and terrifying alien beasts. Antarctica, Alaska and Northern Europe have fallen under the control of the Migou aliens and their advanced technological war machine.

All of the oceans and most of the coasts of the world are sparsely controlled by the Esoteric Order of Dagon, who use sea beasts, monstrous Deep One and Hybrid soldiers, brainwashed or conscripted humans, and their own brand of oceanic mecha in their search for R'lyeh, the lost underwater city of Cthulhu. Civilization has also been infiltrated by the Children of Chaos in the form of the Chrysalis Corporation, slowly extending its grip over humanity.

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