Sydney returns to SD-6 and is assigned with Dixon to travel to Moscow to retrieve some stolen files. But when Sydney discovers that she has inadvertently given SD-6 access to a nuclear weapon, she is forced to travel to Cairo and face a deadly foe. Meanwhile, Will begins to question the circumstances surrounding Danny's death, and Sydney learns of her father's involvement in the murder.

Sydney's life is in mortal danger as she is sent to Madrid to retrieve a 500-year-old sketch that contains a set of numbers and meets up with her deadly nemesis, K-Directorate agent Anna Espinosa. Meanwhile, Will delves deeper into the cause of Danny's death and discovers a very strange anomaly.

Sydney and Dixon go on a dangerous case involving the safety of the United Commerce Organization. Francie confronts Charlie about his secret date with another woman, and Will continues to get closer to the truth about Danny's murder.

Sydney goes undercover in a mental institution to get information from Shepard, a man who has been unconsciously programmed to be a deadly assassin. Meanwhile, after Sydney becomes convinced that her father was responsible for the death of her mother 20 years earlier. Will discovers the true identity of the woman who claimed having an affair with Danny and Francie is relieved to learn that Charlie is not having an affair other woman. Marshall finds the computer worm planted in the SD-6 mainframe by the CIA.

While helping Shepard escape from the asylum in Bucharest, Sydney discovers the shocking connection he has with her past. Meanwhile, after tracking the computer virus secretly planted by the CIA, Sloane is confronted by Alliance representative Alain Christophe, who suggests that one or more moles may have infiltrated SD-6. Will continues to investigate the woman claiming to be Danny's mistress and Sydney finds out the truth about her father's involvement in her mother's death 20 years earlier.

Sydney and Dixon are sent to Las Vegas to gather information from a K-Directorate agent who has ties to the group that attacked and nearly destroyed SD-6. Meanwhile, Sydney learns some shocking news about Francie's fiancé, Charlie, Will begins his journey in discovering what SD-6 really is, and Jack continues to try to be more of a father to Sydney when he helps her decide whether or not to continue with graduate school.