Goddess of Victory: Nikke takes place in a post-apocalyptic future where the Earth was suddenly attacked by unknown mechanical creatures called Raptures that destroyed everything on the surface, forcing the remaining humans to take refuge underground and establish the Ark, a metropolis ruled by the Central Government. The manufacturers Elysion, Missilis Industry and Tetra Line—owned by Ingrid, Syuen and Mustang, respectively—that compose the Big Three work on converting women and children into powerful obedient soldiers called Nikkes to be used as a weapon to defeat the Raptures and restore humanity on the surface. Due to their prominence, the Big Three CEOs have very high authority; they are, however, heavily monitored by the Central Government to prevent any hostile behavior.

The story is played from the perspective of the Commander who graduated from the Military Academy one day prior to the events of the game; despite this, he performs extraordinarily in his operations and survives various encounters with rare Rapture species throughout his journey. He leads a squad called Counters, which consists of the Nikkes Anis, Rapi and later down the story, Neon. The Commander views Nikkes with sympathy and privately advocates for Nikke rights, which is illegal in accordance with the laws of the Ark. Outlaws may be sent to the Rehabilitation Center or the Outer Rim, an area fully isolated from the rest of the Ark, and they have formed terrorist organizations claiming to fight for human rights for themselves.