Ex-FBI agent Will Graham has an uncanny ability to empathize with psychopaths, allowing him to understand their motives. However, this skill comes at the cost of his mental and emotional stability. After a near-fatal encounter with the notorious Hannibal Lecter during an investigation, Graham retires to Florida. But his peace is short-lived as the FBI seeks his help again to catch a new killer nicknamed "The Tooth Fairy," who has murdered entire families during sequential full moons. Feeling an obligation to prevent further deaths, Graham reluctantly agrees to come out of retirement. To aid in his investigation, he must confront the demons of his past and seek insights from Lecter, now a manipulative captive in a high-security asylum.

Graham's investigation leads him to uncover patterns in the Tooth Fairy's offenses, which are influenced by the lunar cycle, causing a time-sensitive race to stop the next murder. As Graham delves more deeply into the case, the psychological toll intensifies, with Lecter playing mind games from his cell, and the new killer, who is harboring a complex and tortured psyche, further complicating matters. The investigation becomes a twisted journey as Graham strives to understand the killer's motives and Lecter's cryptic clues while trying to hold onto his own sanity. His detective work points him towards the discovery of a troubled individual with a deeply disturbing connection to his crimes, as Graham employs unorthodox methods to try and predict the killer's next move.