Uberich Advent Sinners tells the story of a man named Joe, whose world is collapsing after a series of paranormal events. A girl named Chava, who has physical abilities, wants to eliminate him, because her cult believes Joe is the key to dominating the reality between worlds. The conflict begins when a shadow attacks the protagonist and his ex-girlfriend Reina in an alley, after which they are rescued. Soon, a woman in a black dress attacks their home with energy blasts, forcing another personality named Annie to intervene and lead the group to the Ange Defense Research Institute to uncover the truth. Joe's initial indifference to what is happening ends when he discovers a tracking device on himself, proving that escape is impossible. In the basement laboratory of the institute, the group uncovers a secret that connects their attacker, a space blockade, and a high-orbit station.