Upon returning home after preventing a second Xindi attack, Enterprise explores cultural shifts on Vulcan; forges alliances with Earth's neighbors in the face of Romulan aggression; deals with a plague inside the Klingon Empire; explores the Mirror Universe; and overcomes xenophobic elements to lead an interstellar community.
When genetic supermen left over from the Eugenics Wars hijack a Klingon ship, Archer must rely on their creator, the criminal Dr. Arik Soong, to help hunt them down.
Arik Soong leads his band of Augments to a medical facility where hundreds of genetically enhanced embryos are still stored, intending to retrieve them and bring them to life.
Earth's embassy on Vulcan is bombed, and the ensuing investigation puts Archer and T'Pol on the trail of a Vulcan religious faction hiding in a treacherous desert.
Archer, T'Pol and T'Pau attempt to bring the Kir'Shara — an artifact believed to contain Surak's original writings — to the Vulcan capital, as the NX-01 gets involved in a Vulcan-Andorian military clash.
Archer visits Shran's icy homeworld to find an Andorian subspecies called the Aenar, to determine their connection to the marauder destroying ships in the region.
While Enterprise visits Earth for the launch of Columbia, Phlox is kidnapped and forced to help the Klingons deal with a grave threat toward their species.
Six years in the future, an emotional Captain Archer and the crew return to Earth to face the decommission of Enterprise and signing of the Federation charter.