The series centers around the adventures of three teenage girls - Sam, Alex and Clover - who live a double life as spies working for the World Organization of Human Protection (WOOHP). The girls are recruited by the organization's leader, Jerry Lewis, to solve crises that arise around the world. Many of their missions involve dealing with disgruntled villains who have been wronged in some form during their past. Several have exacted revenge on the spies by invading their personal lives. The b-stories focus on the girls' daytime lives as high school students, dealing with relationships, school and school rivals.