When the menace of Castor rears its head once more, Sarah and her entire family must come together to survive.

Castor pursues the Leda clones for original tissue samples. Helena, who is pregnant and imprisoned, is examined by a mysterious new villain. The Castor boys are also out to play, toying with a frightened young woman, Patty, in a sexy switcheroo that ultimately sets Sarah – and Art – hot on the Castor trail. But it’s not all fun and games for the Castor boys, as Sarah gleans they may have a mysterious defect that puts their lives in peril.

Leda and Castor are both on the hunt for original clone DNA. On-the-lam, Mark and Gracie pursue new leads to find the samples that might set them free, while Art and Sarah reunite to track them down. Meanwhile, Cosima and Scott try to learn more about Castor’s biology and Alison’s new money-making venture is going gangbusters. A shocking revelation about the Castor-Leda connection leaves the sisters reeling, just before Sarah witnesses a deadly Prolethean-Castor face-off.

Mark is taken down in a Prolethean shoot-out and Sarah must step in to help. But as Sarah gathers intel that puts her on the trail of the original Castor DNA, a familiar foe is not far behind. While Helena continues to toil in a faraway military compound, it is ultimately Sarah’s fate that will hang in the balance as she tries to save her sister. Meanwhile, Gracie is cast out from the Prolethean fold, and Alison and Donnie come face-to-face with unhappy drug lord, Jason Kellerman.

Helena and Sarah are reunited at the Castor camp. As Sarah suffers testing, Paul appears to chide her; but his allegiances are beginning to strain. While the Leda family worries about Sarah’s absence, Gracie ‘breaks loose’ under the care of Mrs. S and an unwilling Felix. Cosima falls hard for an internet date, Shay.

Paul digs and finds the ugly truth behind the Castor Boys’ logbooks of names, pushing him into action. Meanwhile, Felix is desperate for info on Sarah’s whereabouts, and presses the still-ailing Rachel for any shred of a lead. In order for Donnie and Alison to take their money-making endeavor to the “next level” she must introduce Jason Kellerman to her unique business plan.

When Rachel makes a promise to Sarah, it comes with a hefty price. Meanwhile, Helena and Gracie work with the Hendrixes, and Donnie takes Kellerman to task. Over at Castor, Coady and Benchman scheme to track down the Castor Original, and Rudy descends on DYAD for a much needed asset.

Sarah, Felix, and Mrs. S are in London to track down the Castor Original, but their enemies are not far behind.

Castor and Topside force Sarah to make uneasy alliances. But there is some rest for the wicked, when Donnie gives Helena an unexpected ‘gift’, and the results of Alison’s candidacy finally come in. Even as team Leda takes a moment to breathe, change is afoot and a life hangs in the balance.

Following up on intel from a mysterious source, Mrs. S heads on the road with Sarah to investigate a lead on a Neolution defector. Meanwhile, an unexpected reunion takes place on the island, while Cosima's research leads her to a discovery more terrible than she could have ever imagined. As more pieces slide into place, the puzzle only seems to become more complicated.

Cosima is forced into an alliance when an old enemy returns to the island, accelerating P. T. Westmorland's sinister agenda. Meanwhile, on the mainland, Krystal stumbles onto a vital clue to the Neolution endgame. Sarah and Mrs. S’s research into Neolution's corporate ties leads to the cosmetics industry and an inevitable cross with Krystal Goderitch. But before Sarah can dig deeper, Krystal hijacks the investigation.

As P. T. Westmorland demands a more aggressive action on Kira, and Sarah fights to save her daughter, Rachel discovers a dark secret that makes her question her place within Neolution. Meanwhile, Cosima has returned with a vital clue to Westmorland's true identity.

Mrs. S orders the sisters to take a night off from sleuthing to celebrate Felix's art opening. But while Felix attempts to impress a famous gallerist with the help of his sestras, Sarah remains on edge with a nagging suspicion that S is hiding something. Meanwhile, wounded and desperate, Rachel reunites with an old ally, but their plans for revenge on Neolution put Clone Club in the line of fire.

A devastating loss is eclipsed when word reaches Sarah that Helena has been kidnapped. Clone Club bands together in a race against time, determined to find her before she has her babies. And with time running out, Sarah is forced into action in a last-ditch effort to save her sestra.

With Helena forced to take shelter behind enemy lines, it’s a bloody last stand for survival as Sarah and Art struggle to protect her, and end the siege on the sestras once and for all.