Set in the future, the plot follows Zouichi Kanoe and his AI companion Fuyu Kanoe, whose luminous form is integrated into the system of his motorcycle. They are agents sent by Toha Heavy Industries to retrieve humans with the ability to resist and transmute the N5S infection, which is spreading across the world, turning humans into "Drones"; disfigured, zombie-like beings.
Biomega is the second prequel to BLAME! and is the story of how the world in BLAME! became shrouded by the Megastructure.