After the devastating bloodbath at Lecters home Hannibal establishes a new life for himself in Italy along with the company of his own psychiatrist Bedelia.
Will travels to Lithuania where he gains a new ally in his search for Hannibal Lecter while Jack Crawford makes his way to Italy with some searching of his own
Dr. Fredrick Chilton is alive and well, if not somewhat reconstructed, urging those wronged by Hannibal Lecter to use Will Graham as bait to flush him out.
Hannibal has been imprisoned for three years at the Baltimore State Hospital when a new villain emerges in one Francis Dolarhyde. Jack reaches out to Will to help him track down the brutal serial killer.
The search for serial killer Francis Dolarhyde heats up as Will delves into dangerous territory. He envisions himself in Dolarhyde's psyche and contacts Hannibal Lecter for help in profiling the killer.
Carvings symbolizing the Great Red Dragon are retrieved from crime scenes, casting light on Francis Dolarhyde's warped psyche. Meanwhile, both Dolarhyde and Will seek the wisdom of Hannibal Lecter.
With a full moon approaching, Jack and Will are certain that Francis Dolarhyde will strike again but they lack a solid lead; Alana gives Hannibal a chance for redemption.
Will hatches a cunning plot to slay Francis Dolarhyde, using Hannibal Lecter in his ploy. Bedelia voices concern about the perilous plan as Will continues his game with Hannibal, though Will may have to face his darkest fears.