A young girl stands on top of a building in Shinjuku as she receives a call from her handler. The handler congratulates the girl, known as "Glass Heart" with a job well done regarding her latest kill, which her handler refers to as her 50th. Glass Heart recounts the day's events. She had just killed a man sitting on a park bench with a silenced gun. As she was leaving the park, a small girl runs in with some ice cream and Glass Heart realizes that she has just killed the father of a young girl. With that she jumps off the building, impaling her chest on the iron spiked fence below.

At the same time, Kaori Makimura is running late for an appointment to take wedding photos with her husband, the "City Hunter" Ryo Saeba. When she sees a girl about to be run over by a truck, she jumps and pushes the girl out of the way before the truck hits her. A short while later, she is declared brain dead and her heart is harvested for organ donation, as she had a donor card on her when she died. However, the Organization, needing a heart for their assassin, steals Kaori's heart while it is in transit and implants it into Glass Heart's body.

Glass Heart is transported to Taiwan, where she remains in a coma for a year. During that time, she is haunted by the images of the people she has killed, along with the images of the donor Kaori as well as Ryo Saeba of whom she does not know. She wakes up after one year to find out who these people are. She travels back to Shinjuku, and after several close events, manages to track down the "City Hunter". He has retired from his role since his wife's death. Upon finding that Glass Heart is the recipient of Kaori's heart, Ryo decides to adopt her as his daughter, and is also given a name provided by her real father: Xiang Ying. The former mercenary now tries to help the former assassin move on with a normal life in the outside world.