You Are Empty takes place in 1955 in alternative Soviet Union, where Joseph Stalin still reigns. In an attempt to ensure the global victory of Communism, the government has constructed a massive psychic antenna to broadcast a reality-altering signal designed to transform the population of the Soviet Union into supermen. However, the experiment goes horribly wrong, and most of the population is either killed or transformed into homicidal mutants.

In this game you play as the medium–ranking soldier who has an accident at his place of work. While he is unconscious, something happens and when he wakes up in a hospital he finds many homicidal mutants and the world in ruin. He fights with many homicidal mutants and investigates. He rarely meets with other survivors and encounters many surviving soldiers of the Red Army that are hostile to him and attempt to bring him to the high-ranking soldier who tells him about the backstory behind this calamity before committing suicide.