Sydney is grateful and proud of her father after he saves her life while on a case in Havana. But her admiration is short lived when Vaughn discovers further evidence that Jack may have been responsible for the deaths of over a dozen CIA officers many years earlier.

Vaughn disobeys orders and attempts to help Sydney and Jack avert the destruction of SD-6 headquarters and all its occupants. Meanwhile, McKenas Cole continues his vendetta against Sloane and searches for a mysterious device. A desperate but determined woman convince Will to continue his investigation of SD-6 and the imprisonment of David McNeil.

Sydney is tested by the DSR to discover her mysterious link to a chilling 500-year-old picture and prophecy foretold in a Rambaldi manuscript. Meanwhile, after uncovering the identity of the rogue group leader, "The Man," Sloane learns through fellow Alliance of Twelve member Edward Poole that a close friend may be in cahoots with the enemy.

In order to catch Khasinau and get closer to finding her mother, Sydney and Vaughn set up an undercover transaction for a Rambaldi artifact with Khasinau's representative, Mr. Sark. But Sydney's cover may be compromised when a SD-6 agent is sent in to thwart the sale. Meanwhile, Will is enticed to continue his investigation of SD-6 when he learns the identity of one of his kidnappers. Emily tells Sydney that she knows about SD-6, which forces Sloane to make the most difficult decision of his life.

In order to save Will's life, Sydney and Vaughn must destroy a familiar looking Rambaldi device, while Jack makes a risky deal with Khasinau's representative, Mr. Sark. Meanwhile, the CIA believes that one of their own is a mole for "The Man"; the Alliance comes to a decision regarding the fate of Emily Sloane; Dixon's suspicions about Sydney intensify; and Sydney finds herself face-to-face with "The Man."

Sydney's trust in her father begins to fade. Meanwhile, Sydney and Vaughn may have been exposed to a deadly virus while in Taipei; Sloane haunted by Emily's death begins to unravel. Vaughn enlists Will to help research a case.

The entire APO gang is trapped inside the CIA offices and Weiss saves them. However, Weiss will not be returning to APO, he will just be helping the others on a mission to obtain information regarding Sydney.

Sydney gives birth to the baby, but Sloane may need something from the newborn. Nadia awakens.