The game takes place in a post-apocalyptic 28th century. In the mid-22nd century, tensions rose between an expanded Chinese Empire and a joint European/North American Federation of the Free World. The unexplained apparent destruction of the first Chinese interstellar colony ship resulted in China launching devastating nuclear strikes with stealth missiles. In retaliation, the American president gave the command to counter strike with cold fusion long-range missiles. World War III started on February 17, 2143; it lasted less than 6 hours.

It took over three centuries for even the most rudimentary civilization to return. By the mid-26th century two great cities had risen from the ashes, thanks in large part to the "Ceres Project". Originally an MIT project in the early 21st century aimed at storing every aspect of human knowledge on holodisk, it had been taken over by the American military in response to the murder of the project leader.

500 years later, both cities are now but shadows of their former selves: Neocron is diminished thanks to a succession of coups d'état as well as a mass exodus to Irata III, a colony 80 light years away formed by the missing Chinese colony ship, and Dome of York suffers from losing a devastating war with Neocron.