In the near future, Major Mira Killian is the first of her kind: A human saved from a terrible crash, who is cyber-enhanced to be a perfect soldier devoted to stopping the world's most dangerous criminals.

When Guy, a bank teller, learns that he is a non-player character in a bloodthirsty, open-world video game, he goes on to become the hero of the story and takes the responsibility of saving the world.

The prologue of the film acknowledges the events of the Godzilla (1954 film) (using the 1954 Godzilla monster rather than a successor Godzilla), while inventing its own timeline, explaining that the Oxygen Destroyer was never used here and that the capital of Japan was moved from Tokyo to Osaka. The film takes place in an alternate universe with advanced technology, explaining that in 1966, Godzilla attacks the first Japanese nuclear plant in Tokai, Ibaraki, Ibaraki Prefecture. After this, the G-Graspers, a section of Japanese Self Defence Force, was dedicated to fight Godzilla. In 1996, clean plasma energy replaced nuclear energy, but this did not deter Godzilla from attacking. Plasma energy is also banned, due to the fact that Godzilla attacked the original plasma energy Fusion power.

In 2004, Mechagodzilla is undergoing repair modifications after its battle with Godzilla one year earlier. Prime Minister Hayato Igarashi accepts Lead Scientist Yoshito Chujo's choice to replace the Absolute Zero Cannon with a powerful Tri-Maser.