As the team retrieves a data cache attached to the necklace that Jane wore, the data shows Jane's poisoning as severe symptoms take a toll on her. Meanwhile, the FBI team chases a dangerous enemy operative, and a new enemy emerges in the figure of Zapata who tries to control her father's company.
A mural in the FBI office leads the team to a Russian spy. Jane bargains with the spy to provide her with files of CIA black sites. Burke and Zapata travel to Stockholm to retrieve a hard drive with the company's files on it, and Burke murders Kira. Jane prepares a lethal poison to use on Weller.
When a major threat emerges in the form of two different explosions, the team has to interfere in time to prevent them. It turns out Burke is the one who ordered for the explosions and reported them to the FBI to gain the trust of the public media. Jane is unable to use the poison on Weller.
Weller learns that the woman Jane has met before is called Violet Parks. When a tattoo leads the team to an abandoned hospital, they find porcelain dolls there. When an examination of these dolls is carried out, it's revealed they have a deadly pathogen, leaving the whole building in quarantine.
For the next mission, a tattoo leads the team to a notorious assassin who works for a terrorist group that threatens to wage an attack on New York City. As Jane encourages Weller to ask Keaton to help with the mission, the latter is shot, but the attack is foiled.
When a tattoo points to someone from Weitz's past, the team is drawn into a dangerous political plot. Reade is fired giving his FBI password to Zapata, but Weitz soon reveals that he wants Reade on a mission to bring Zapata down.
When Eve tries to retrieve an item from the FBI facility, Kurt uses the devices to blow up the item. Patterson and Rich solve a mystery at the FBI. As they find one of Roman's data caches, they find medical information that can help cure Jane.
Weller tells Patterson and Rich that Jane is back to being Remi. When NORAD is informed of a missile headed for New York and spreading anxiety, the team learns that NORAD was hacked. Jane manages to break Shepherd out. Zapata tries to get Del Toro from Mexico, but Reade and Weitz corner her.
The team tries to get Jane back to her self. When Weller uses a needle to sedate her, the doctor is brought to carry through with the remedying procedure found in Roman's data. Jane wakes up after convincing Shepherd that Remi is their enemy. Jane shoots Sheperd dead when the latter attacks Weller.
When the team learns that Nora is alive as Roman sent her into hiding to save her, she reveals that the stem cells Roman kept to cure Jane were destroyed in an attack. Zapata is forced to confess that she was sent to stir discord in the HCI Global. In Toronto, Zapata is captured by the CIA.
As a best-selling crime author is murdered, the team learns that his latest manuscript was based on true people, and someone from the FBI has been leaking information to him. As Jane starts to lose her vision, she is kidnapped by the killer, but then she uses the Morse code to deliver a message.
A new data cache leads Patterson and Rich to Ken Lee, who has the stem cells necessary to cure Jane. However, they strike a trade-off with Lee, as he tells them he wants the Book of Secrets in exchange and wants a house arrest. The duo finds the information Roman couldn't find, and Jane is cured.
The team must stop Madeline Burke's plans to bomb a building and crash an airplane.
A suicide terrorist compels the team to look into a case from their past.
Jane's past with Shepherd and Sandstorm causes a lot of trouble for the federal team. When a tattoo leads the team about the robbery of a box full of plutonium, it turns out the terrorists intend to sell the box to Cameron, who wants to use it to dentate a military meeting to avenge his firing.
Jane asks her old enemy, Borden, for help to atone for her sins as Remi. Meanwhile, a hitman targets the HCI Global heads to avenge Del Toro's death. The FBI is chasing Madeline, while Jane is sedated and abducted.
The team races against time to save Jane from a deadly plot that has her buried in a wooden box. Zapata threatens Burke, using information she knows about her son's indiscretions. Burke's lawyer instructs Masters to proceed with Helios.
As a tattoo points to a deadly bacteria that caused numerous deaths, the team reaches Patterson's father. Claudia calls Zapata to find any information about Masters, but Claudia is later found dead. Jane and Weller continue their search for the hooded figure, and a sketch reveals Weller's mother.
The team discovers an international plot when a lethal weapon is stolen. As Jane and Weller meet Weller's mother, she reveals she had known Shepherd. At Jane's recommendation, Weller makes peace with his mother and admits her into rehab.
The team faces a terrifying challenge as Sho tries to deceive them once more in an attempt to escape prison. Meanwhile, Zapata and Reade try to deal with their living conditions.
Dominic begins to put Madeline's plan into effect. Burke remains uncooperative as she is called in for questioning, but she eventually gives them Masters's phone number. Meanwhile, a virus spreads into the Eastern Seaboard, and when the power is cut off, the country sinks into chaos.
The team begins an international mission to prevent the spread of an attack and control the situation. When they are subjected to a plan that seeks to incriminate them, the team is saved as they meet up in a remote cottage. Nash plans a vengeful strike on the cottage, and only Jane is saved.