Steins;Gate 0 takes place after a hypothetical bad ending to Steins;Gate, where main character Rintaro Okabe fails to save the life of Kurisu Makise after travelling back in time and gives up. Zero follows the consequence of Rintaro's choice and the effects it has in the world, as World War III draws closer with each passing day.

Several months later, Rintaro attends a lecture by Alexis Leskinen and Maho Hiyajo, from Viktor Chondria University, the university at which Kurisu worked. There, he is presented the project Amadeus, an advanced artificial intelligence capable of replicating a person based on their memories, by using Kurisu's previously published thesis as a basis.

Upon getting to meet Maho Hiyajo and Dr. Leskinen, Rintaro is presented with the opportunity to act as a tester for Amadeus, or, more precisely, a version of Amadeus that uses the memories of the deceased Kurisu Makise.