After the shocking events of the Season 2 finale, Hannibal is on the run in Europe - accompanied by his psychiatrist Bedelia Du Maurier - sporting a new identity, but servicing the same insatiable appetite. As the lives of Will, Jack and Alana converge toward Hannibal again, each with their own motivations to catch him once and for all, their deadly dance turns in startling and unexpected ways.

After being sworn in by Jack Crawford, the head of the FBI Behavioral Science Unit, to help capture a serial killer who is on the rampage, Will finds himself increasingly struggling to control his thought processes that inform his uncanny ability to empathise with serial killers. When damning evidence shows up at the FBI that implicates Will in a string of grisly murders he is immediately placed under the care of the Baltimore State Hospital for the Criminally Insane. As Will tries to assure Jack of his innocence he also attempts to convince him of the identity of the real killer.

After a particularly grueling case hunting a serial killer known as the Minnesota Shrike, Will Graham threatens to walk away. Jack Crawford, the head of the FBI's Behavioral Science Unit, desperately needs Will on his team to break the tough cases, so he enlists Dr. Hannibal Lecter, to ensure Will's mental well-being. Unbeknownst to Will, Hannibal also has a particular insight into these horrible crimes and the psychopaths who commit them. As Will hunts down brutal killers, he is unknowingly sitting across from the most gifted killer of them all.

Eve is a bored, whip-smart, pay-grade MI5 security officer whose desk-bound job doesn't fulfill her fantasies of being a spy. Villanelle is a mercurial, talented killer who clings to the luxuries her violent job affords her. Everything changes when they cross paths.

马蒂（伍迪·哈里森 饰）和拉斯特（马修·麦康纳 饰）是一对合作多年的搭档，马蒂为人开朗圆滑，在警局的同事里很吃得开，而拉斯特则恰恰相反，他性格孤僻沉默寡言，沉浸在自己的世界中无法自拔。然而，令马蒂感到十分钦佩的是，拉斯特拥有极为敏锐强大的观察力、判断力和逻辑推理能力，许多疑难杂案一经他手，便能够被轻松化解。 尽管马蒂是唯一一个能够受得了拉斯特的人，但两人的合作和友谊却依然产生了无法弥补的裂缝，其原因要归结到1995年所发生的一起神秘古怪的宗教杀人案件之中。如今已经是2012年了，当早已不再联系的两人因为这起案件又重新走到一起之时，会有怎样的真相在等待着他们呢？