Based in Shinjuku, Ryo Saeba, a talented disposal shop "City Hunter" who solves various requests, and his partner, Kaori Makimura, are asked by a female video creator, Angie, to find an escaped cat. A request comes in. Meanwhile, Saeko Nogami of the Metropolitan Police Department, with the help of Umibozu and Miki, begins an investigation into the invention of the biotech company Zoltic. The invention is a terrifying drug that transforms soldiers on the battlefield into superhumans, and is the latest version of the "Angel Dust" that once devoured Ryo and killed her partner, Hideyuki Makimura.