In 2021, a parasitic virus called "Gastrea" infects humans, transforming them into monsters. The remnants of humanity now reside within the Monolith walls, which are constructed from Varanium, the sole substance capable of harming Gastrea. To combat the threat posed by Gastrea, "Cursed Children"—girls whose bodies harbor trace amounts of the virus, granting them superhuman powers—are officially designated as Initiators by the Tendo Civil Security. They are paired with Promoters, individuals tasked with guiding and protecting these young Initiators. These two-person teams are dispatched on missions to battle the monsters spawned by the Gastrea virus and keep them contained. Black Bullet centers on the team of Enju Aihara, an Initiator, and Satomi Rentaro, a Promoter, as they undertake missions to fight the escalating Gastrea threat in their hometown of Tokyo.