The film begins with Kiddo, a pregnant bride, being betrayed by her teammates and left for dead by Bill. After a four-year coma, Kiddo awakens and sets out on a quest for revenge against her former teammates, taking on each of them in a series of intense battles. Along the way, she encounters other characters, including O-Ren Ishii (Lucy Liu), a former assassin and current leader of the Tokyo crime syndicate, and Vernita Green (Vivica A. Fox), a former DVAS member turned suburban housewife.