Four months after Vaughn's murder by the traitorous Gordon Dean and his associate Ivan Curtis, a grief-stricken Sydney teams up with Renée Rienne, a French freelance assassin and fugitive on the CIA's most wanted list who knew Vaughn from their past association with Prophet Five, to ask for leads in order to track down the killers before they can strike again. Meanwhile, Jack enlists a reluctant new agent, Thomas Grace, as Vaughn's replacement at APO, and Weiss struggles to decide whether or not to accept a promotion that would force him to move to Washington D.C. and leave his colleagues at APO. During this time, Sydney, Dixon and Weiss travel to Amsterdam to track down Curtis who is in the process of buying a potential weapon.

When Kelly Peyton steals some software from a CIA warehouse concerning the late Michael Vaughn, Sydney is soon abducted by Prophet Five agents where she is subjected to a hypnotic state making her flash back to her happier times with Vaughn in order to learn where a supposedly powerful device, called The Horizon, is located. Meanwhile, Jack must team up with Renée to locate Sydney when they captured and torture Aldo Desantis, while the mastermind behind Prophet Five is finally revealed... and why the person has a strong interest in Sydney's unborn daughter.

After escaping from Peyton and her henchmen, and learning she's on a freighter at sea, Sydney goes to the communications room and sends a message to APO routed through the CIA to her whereabouts. Unbeknownst to her, the message is intercepted by a mole at the CIA working for Prophet Five, although APO was able to obtain a piece of the transmission. Wanting to retrieve Sydney, the APO team, Rachel, Tom, Dixon, and Marshall attempt to break into a secured server room located at Langley with the goal of obtaining the remaining part of the transmission. Problems arise, however, when APO is forced to take the hard drive, which triggers an alarm. They manage to escape the situation thanks to former APO agent Eric Weiss who aids them in sneaking past the guards. Although the transmission on the hard drive is corrupted, APO is able to learn who corrupted it. Jack sets a meeting up with the division heads of the CIA and is quickly able to identify the mole. Meanwhile, Tom is revealed to have another agenda when he obtains information about a certain Allan Korman, who was a former German assassin now in a witness relocation program, and who murdered Tom's wife many years earlier.