The movie opens with the assassination of a man of unknown identity. A team of three CIA officers, including rookie Jack Chen, watch through surveillance as an assassin named Fiona Birch enters the man’s heavily guarded apartment suite and, after having sex with him, kills him by breaking his spine with her bare hands during a massage.
As she escapes, Fiona’s car is hit by a rocket. As the CIA officers rush to extricate her from the wreckage, they are shot and killed by a woman in a limousine, leaving Jack as the only survivor.
The woman in the limousine is revealed to be Madam M, the leader of a mysterious assassin organization. After the incident, young girls across the globe start disappearing one after another. The only relationship among them is that they are all trained in martial arts or sports. As Jack correctly theorizes, these girls have been abducted by Madam M and transported to an island to be trained to become professional assassins. After six years of gruesome training, only Charlene Ching, Katherine, and Jing survive and “graduate.” The last test in order for them to graduate was a fight to the death test. Katherine and Charlene, being friends, could not kill each other, and so each is accepted as a survivor. To celebrate, Madam M gives them all wines that have drugs in them. As the drugs take effect, Madam M calls her guards to rape the girls, thus (in Madam M’s words) making them ready for what was to come.
The three girls are then sent on several missions around the world. During one of her missions in Hong Kong, Charlene runs into her long-lost mother, Faye Ching. Jack tracks Charlene down, but Charlene manages to knock him out and escape. Believing she would return to see her mother, Jack waits outside Faye’s house. However, Jing arrives before Charlene and stabs Faye. Jack tries to fend her off but fails. Charlene shows up and kills Jing after a fierce fight. She and Jack then escort the wounded Faye to the hospital.
To regain their freedom, Charlene and Katherine accept a final mission from Madam M. A yakuza boss, Ryuichi, has contracted Madam M to eliminate a traitor in his gang. The mission turns out to be Ryuichi’s trap to avenge his partner, who was assassinated previously by one of Madam M’s girls (Charlene). Ryuichi kills Madam M and captures Katherine, though Charlene escapes.
While Jack is at the hospital, Charlene calls him to meet her at the beach. They have sex, and the next morning, she leaves a note in his shoe saying that if they are destined, they will meet again. When Charlene returns the next day to rescue Katherine, she watches helplessly through a bullet-proof glass as Katherine, after being tortured, is killed. Charlene battles Ryuichi and finally kills him.
Jack and Faye are at a Chinese temple offering prayers. Faye jokingly says that the prayers must be nonsense in Jack’s point of view. Jack tells her that although he never had a religion, he feels peace every time he is in the temple. Faye commends his behavior and says he should visit the temple more often. Meanwhile, Charlene is in a different temple praying for Katherine’s soul to rest in peace, and she tells the deity that she wishes to be with the one she truly loves, Jack.
Jack claims at the end of the movie that there are times when he is sure that Charlene is beside him; the last scene of the movie is Charlene watching him rush through the crowd looking for her.