After the horrifying revelations and reversals of fortune in Baltimore, Chandler and his fractured team join forces with an underground resistance in an attempt to defeat Amy Granderson. With doses of the cure running low, Rachel tries to do some good for the sick while remaining a prisoner at Avocet.
Slattery and the crew of Nathan James are in a race against time to save an injured Dr. Tophet and regain control of their ship.
Nathan James returns home to Norfolk on a mission. With his family now safely aboard the James, Chandler sends his crew in search of their friends and loved ones.
The crew of Nathan James discovers that hospital ship USNS Solace was sent to sea to wait for Dr. Scott's cure. Captain Chandler sees an opportunity to add another ship to their fleet while Rachel is eager to find a lab better equipped to replicate the vaccine. When Solace fails to respond to radio communications, Chandler and his team board the ship... and come face-to-face with an unexpected enemy.
With a small group of survivors from Solace in tow, Chandler and his crew square off against an enemy of the most dangerous kind - a nuclear-powered submarine led by rogue British naval officers, Sean and Ned Ramsey. XO Slattery interrogates a captured mercenary from the hospital ship in an effort to extract information on the sub and its mission. As Nathan James engages in a perilous game of cat-and- mouse, the truth about the mercenary sub unfolds.
Chandler tracks a new threat to Northern Florida. Meanwhile, Rachel comes across a secret formula that her mentor, Dr. Hunter, had been perfecting.
While XO Slattery struggles to evade the sub in the water, Chandler and the land team infiltrate the Immune compound. Danny poses as one of Ned's workers and discovers that Niels, a.k.a. Patient Zero, is now working for the Ramseys. Meanwhile, Captain Chandler manages to encroach on Sean's inner circle, which includes an important government official, Jeffrey Michener. Has Michener been brainwashed by the Immune propaganda along with the rest of the camp? Or can he be an ally?.
Still trying to piece together Dr. Hunter's lost formula, Rachel grapples with the fact that Niels, her sworn enemy, is now on board Nathan James, while Chandler works to gain intel and reverse the brainwashing Michener suffered at the hands of the Ramseys.
Chandler and the team attempt to find supplies and materials for Dr. Scott's lab, but run into bounty hunters and the Immunes. Rachel's effort to find a spreadable cure depends on the scientist who nearly killed off mankind.
A suspicious death on the ship causes Chandler to start a hug investigation. Rachel works on a more efficient cure. Alisha manages to decode an Immune message. The ship makes its way to New Orleans.
After a message is broadcast implicating the Navy in a devastating disaster, Chandler looks to infiltrate the network and regain the trust of the American people.
After retrieving the mastermind behind the Immune communications network, Nathan James finds itself trapped between the sub and civilian blockades set up by the Immunes. Chandler sends Dr. Scott and the cure off the ship under the protection of XO Slattery as the James heads towards its inevitable final showdown with the sub.
With their mission now fully dedicated to spreading the cure, Nathan James puts a call out to civilians to meet at pre-selected ports across the country.