In the season 3 premiere of Penny Dreadful; Ethan is a prisoner under Inspector Rusk's watch heading through America. Sir Malcolm meets a mysterious native american while in Africa. Frankenstein gets a visit from an old friend: Dr. Jekyl. Vanessa seeks the help of a very intriguing and interesting doctor.
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.
Vanessa contacts her old friend Ferdinand Lyle for help. Lyle introduces her to Catriona Hartdegen. Lily, Dorian and Justine put their plan in motion. Ethan, Sir Malcolm and Hecate arrive at Talbot's ranch.