Odyssey has survived her initial battle with the Archeins. But with her crew decimated, and her new captain unsure of himself, the fight for survival has reached a crucial stage, as Odyssey's antimatter stores have been depleted through an emergency pod dump. When an attempt to obtain replacement supplies takes a turn for the worse, Ro must balance his desire to protect his crew with the knowledge that without fuel, none of them will survive.

The battle against the Tholians has been long since over, and the Federation enjoys peace within its borders once more. But in an uninhabited section of Romulan space, a new threat is brewing. Mysterious ships from the Andromeda galaxy have begun an invasion, and seem all but completely unstoppable. But springing forth from the vaults of the secret Grey research facility on Deep Space 12 is one last miracle to help the newly-allied Romulans. Slipstream technology has the ability to enable the newest Federation starship, the USS Odyssey to traverse millions of light years in a matter of weeks. A bold mission is put together to stop the ruthless invading forces, but will it be enough to stop the vastly superior forces?

The Archien's relentless pursuit of the U.S.S. Odyssey is taking its toll and Ro is having to deal with serious differences of opinion amongst his senior staff. Starfleet ideals win out over Romulan practicality as a Starfleet distress signal is detected and Odyssey is steered back into mortal danger to prevent the Archiens from committing genocide. The Archien's internal power struggles escalate as an arrest warrant is issued citing damning evidence against the target. Whose name is on the warrant and what evidence has been found?

Odyssey's newly-formed alliance with the Kelvans threatens to blow wide-open when one of the Kelvan's most revered heroes kidnaps Ro and makes plans to execute him - and Stadi's worst fears are realized when she must accept T'Lorra as the acting Captain of the ship! But while Stadi begins to form a plan to rescue Nevin, T'Lorra must work with the general who kidnapped him in a daring raid on an Archien training outpost - and Ro must once again face his inner demons when an unusual gift passes into his hands from his captors.

Odyssey has struggled in the Andromeda Galaxy for a year. As Ro fights to keep his crew and ship together, a new potential ally emerges. But are the Alosians all that they seem? In the climactic season finale, Seram leads the Archein's on a mission to capture Odyssey, while Caecus searches for his true identity.