The son of Robert Gant (Gregg Henry), director of the Defense Intelligence Agency (DIA), is kidnapped. Former FBI agent Jeremiah Ecks (Antonio Banderas) is asked by his former boss to investigate the case. He discovers that the kidnapper must be one of the Chinese girls the DIA adopts and trains as agents. He also discovers that Gant stole a dangerous nanobot assassin, which operates in the human circulatory system. Gant had placed the nanobot in his son's body in order to smuggle it to North America.
Robert Gant is married to Vinn (Talisa Soto), who was previously married to Ecks. Gant separated Vinn and Ecks by staging the death (by car bomb) of each of them to the other; Vinn was officially declared dead and had a closed-casket funeral attended by Ecks. Also, Gant killed the husband and child of his colleague Sever (Lucy Liu), who subsequently kidnapped Gant's son to avenge herself. It turns out that it is not Gant but Ecks who is the father of the child.
Ecks and Sever succeed in killing Gant. Ecks and his family are reunited.
Out of 102 reviews, the film received zero positive ratings from reviewers.
A score composed by Don Davis was released but a soundtrack was not.
A Game Boy Advance first-person shooter, Ecks vs. Sever, was based on a very early version of the film script and, story wise, is almost nothing like the final rewrite. It was released in 2001, before the film. It was considered an impressive technological feat on the GBA and was much better accepted than the film itself. A second game created after the premier, Ballistic: Ecks vs. Sever, which follows the plot-line from the film, is considered a sequel to the first game.