Emily Byrne (Stana Katic) é uma agente do FBI que assume a difícil missão de capturar um dos assassinos mais perigosos de Boston, mas, durante as investigações, ela acaba desaparecendo sem deixar pistas. Seis anos depois, ela é encontrada quase sem vida e sem memória dentro de uma cabana no meio da floresta. Ao voltar para a sua vida normal, no entanto, Emily descobre que além de seu marido ter se casado com outra mulher, levar uma vida longe de casos criminais será um sonho distante para ela.
Emily is serving out the final days of her FBI suspension while struggling to come to terms with the consequences of her actions from the last two seasons. Hyper-vigilant and distrusting of others, Emily sees threats everywhere and takes a closer look at everyone.
Following the deadly events, Emily must race against time to find and save Nick, with the help of his mysterious informant, Kai. Upon tracking his location, Emily realizes there is a more complex conspiracy afoot and is left to grapple with the possibility that Nick has been killed.
Disoriented and drugged into a paralytic state, Nick wakes up in a dark and confined location. Meanwhile, without a body as proof, Emily refuses to accept that Nick is dead and makes a deal to get him back, only to find that Dawkins has laid a trap and everyone is in danger.
Emily’s demand for the FBI to go after Nick is met with resistance, which leads her to set in motion a risky plan that puts her face-to-face with the one man who can lead her to Nick. Meanwhile somewhere in Europe, Nick is being drugged and psychologically tortured, revealing his buried guilt and his insecurities as an FBI agent, a husband, and as a father.
Emily complies with Dawkins requests in order to be taken to Nick, and orchestrates a clever ruse along the way. Meanwhile, as Nick’s guilt and paranoia threaten to overwhelm him, he finally puts a rest to the personal demons that have haunted him.
Nick continues to be tortured but finds an opportunity to try to escape from his captors. Cal and Emily head off to rescue Nick and become closer along the way. When they reach the mysterious location, they find evidence that links to Nick’s case back in Boston, but there’s no sign of Nick.
Emily makes a final attempt to trade the stolen files for Nick and demands proof that he is alive, unaware that Nick has escaped from his captors in a thrilling chase. Nick makes contact with the FBI, and Emily makes a bold decision to confront Cal about his past.
Emily and Nick devise a plan to infiltrate the refugee camp, and Cal poses as a Meridian guard in hopes of finding Armstrong and bringing him to justice. Meanwhile, Crown and Gunnarsen narrow in on Meridian’s mole and an unexpected visitor arrives at the farm.
Nick works to free the refugees and Cal finally confronts Armstrong. When Gunnarsen and Crown go to arrest Deputy Director Webb, they discover something deadly. Meanwhile, Emily tries to get to the bottom of Elliot’s operation and goes to extreme lengths to protect her family.
Emily and Nick are finally reunited with Flynn back in Boston, but the threat of Elliot’s bioweapon still looms large. Emily resorts to drastic measures and make a dangerous choice to ensure her family’s safety.
