With his wounds now healed, Will Graham heads to Europe eight months after the horrific event that almost took his life, in search of closure with Hannibal Lecter. Meanwhile an Italian inspector thinks that Lecter and a killer he pursued 20 years earlier are the same person.

Will Graham continues his search for Hannibal Lecter, making his way to Hannibal's childhood home in Lithuania. Meanwhile, Jack Crawford arrives in Italy, hoping to find Will and intervene before tragedy strikes again, and Bedelia warns Hannibal against unraveling his new life.

After surviving a disfiguring gunshot, Dr. Fredrick Chilton is now focused on rallying support to capture Hannibal, using Will as bait. Jack is distracted by Bella's failing health, but he implores Will to abandon the risky idea of finding Hannibal. Meanwhile, Alana Bloom entertains a different approach, potentially partnering with Mason Verger to utilize his vast resources.

The hunt for Hannibal begins. Will travels via train with Chiyoh to Florence, as Alanna and Mason use Hannibal's fine tastes to track his whereabouts. Pazzi tries to get in close to find out if Hannibal is the man he's looking for, but his greed may get the better of him.

With Bedelia securing her alibi, Hannibal prepares to leave Florence just as Jack and Will begin to track him down. With Pazzi murdered, Mason and his cohorts consider a different course of action. However, Chiyoh has arrived in Florence with her own agenda.

Captured in Italy by police on Mason Verger's payroll, Will Graham and Hannibal Lecter are delivered to Muskrat Farm to await Mason's revenge. Alana, distressed that Will has been endangered along with Hannibal, plots a rescue. And Hannibal, once again in contact with his old patient Margot, finds it irresistible to remind her that Mason will never make good on his promises. Meanwhile, Jack informs Chiyo of Hannibal's location.

Dr. Hannibal Lecter has been under lock and key for three years at the Baltimore State Hospital for the Criminally Insane, when a new villain arises in Francis Dolarhyde, also known as "The Tooth Fairy." As the investigation unfolds Jack Crawford approaches Will Graham to help catch this vicious serial killer who is targeting families.

The FBI's search for elusive serial killer Francis Dolarhyde intensifies as Will Graham begins envisioning himself in Dolarhyde's tormented psyche. Wading deeper into dangerous territory, Will enlists the help of Hannibal Lecter to assist with the killer's profile. Meanwhile, Alana Bloom reminds Will that the last time that he and Hannibal worked together things didn't end well, but Will sees no other option. Elsewhere, a new woman comes into Dolarhyde's life.

Carvings symbolizing the Great Red Dragon, retrieved from crime scenes, help Will Graham and the FBI shed light on Francis Dolarhyde's disturbing psychology. Meanwhile, Dolarhyde finds ways to communicate directly with Hannibal Lecter regarding his "becoming." Will feels his bond with Hannibal growing uncomfortably stronger, and seeks out Bedelia Du Maurier, the only other person who fully understands the complexities of such a relationship.

Convinced that the Red Dragon will strike at the next full moon, Jack and Will grow desperate, and Alana turns to Hannibal for help.

Will Graham and the FBI enlist the expertise of Dr. Fredrick Chilton in the hopes of luring Francis Dolarhyde into an ambush, using Freddie Lounds as their mouthpiece. As Will's empathy for Dolarhyde begins to affect his fragile psyche, Bedelia Du Maurier warns that the killer Will should be most concerned about at the moment is himself. Meanwhile, Dolarhyde senses that the FBI is closing in and launches a horrifying endgame.

In a desperate bid to slay Francis Dolarhyde, Will Graham engineers a cunning ploy utilizing Hannibal Lecter. Upon learning of his plan, Bedelia Du Maurier voices concerns that Will's actions may not only put his life in peril, but the lives of those around him. As the end draws near, Will remains unflinching in his game with Hannibal-even when it means coming face-to-face with his own darkest fears?