Feeling abandoned and alienated by her faith, a shattered and despondent Vanessa seeks the help of Dr. Seward, an American therapist who has an unconventional way of treatment. Meanwhile, now a prisoner under the watchful eye of Scotland Yard Inspector Rusk, Ethan Chandler is on a train speeding through the desert of the American West. Halfway around the world, in Zanzibar, Sir Malcolm is confronted by a mysterious Native American man named Kaetenay who shares a deep connection with Ethan. Back in London, Dr. Frankenstein seeks out his old friend Dr. Jekyll. With all of her friends scattered around the world facing their own demons, Vanessa is left alone to battle a new evil that has emerged from the shadows.
Lily and Dorian, rescue a young woman. Sir Malcolm continues on his journey with the enigmatic Kaetenay. Meanwhile, Ethan gets some unexpected help from Hecate. Dr. Frankenstein and Dr. Jekyll hatch a plan. Vanessa's relationship with Dr. Sweet grows but, unbeknownst to her, evil forces are tracking her every move.
Ethan and Hecate race across the desert with Sir Malcolm and Kaetenay hot on his trail. The Creature returns to London desperately trying to piece his former life back together. After Dr. Jekyll and Dr. Frankenstein's plan fails, they come up with a new strategy. Lily and Dorian's young acolyte, Justine, demonstrate useful skills. A clue about her past is revealed to Vanessa.
Through hypnosis, Vanessa relives what happened to her in the Banning Institute, including the man who befriended her... and the spirits who tormented her.
Hecate and Ethan travel across the desert, struggling to survive, while the marshals follow them and Malcolm and Kaetenay follow the marshals. In London, Victor and Henry continue their experiments to perfect Henry's serum.
Vanessa turns to an old friend for help, who introduces her to a new ally. Jared has dinner with Ethan, Hecate, Malcolm, Rusk, and Oslow, and invites his son Ethan to do his worse. Meanwhile, Vanessa takes Seward's advice and forms a closer bond with Sweet, while Victor pays Lily and Dorian a visit.
Kaetenay returns to London with Ethan and Malcolm to prevent the darkness that he has foreseen. Meanwhile, Vanessa realizes who Sweet really is, while Caliban is reunited with his family. Elsewhere, Dorian grows bored with Lily's revolution and makes his own plans.
Ethan, Malcolm, and Kaetenay arrive in London only to find it enshrouded in the perpetual night of an endless fog. While they seek out Vanessa, Seward seeks out allies after Renfield turns on her. At Bedlam, Lily begs Victor for mercy.
Season finale. Ethan learns the shocking truth about Kaetenay. Dr. Seward uses hypnosis on Renfield. Meanwhile, The Creature must make a moral decision as Sir Malcolm, Ethan, Kaetenay, Dr. Seward and Catriona battle to save Vanessa.