High-Rise Invasion follows 16-year-old Yuri Honjou, who witnesses a man's head split open with an axe by a masked assailant before fleeing through an abandoned building where every door is mysteriously locked. When she reaches the rooftop, she discovers a silent world of towering high-rises connected by suspension bridges, with no ordinary signs of life anywhere around her. The only inhabitants are masked killers who stalk terrified victims across the rooftops. After learning that her brother Rika Honjou is trapped in this abnormal space as well, Yuri refuses to give in to despair and becomes determined to find him and escape.
As she fights to survive, Yuri encounters other people caught in the same deadly realm, including the capable Mayuko Nise and the mysterious Kuon Shinzaki, while figures such as Sniper Kamen hint that the masks and the world itself obey a larger, ruthless system. Every crossing between buildings can lead to another ambush, and every alliance is shaped by fear, violence, and the constant pressure to kill or be killed. Surrounded by more masked murderers eager to terrorize their prey, Yuri must stay alive long enough to reunite with her brother and challenge the irrational world that has trapped them all.