A series of mysterious deaths pulls Rosewood off the glamorous promenades of South Beach when a troubled young genius stands accused of murder, and the only one who believes in his innocence is Rosewood. He must contend with a colorful new adversary, escalating health problems and a burgeoning romantic relationship, while Villa's inability to connect with people hampers her own ability to investigate the case.

A bounty hunter who happens to be Hornstock's former partner helps Rosewood and Villa track a murderer; Pippy receives an opportunity that could launch her music career; Villa attempts to reconnect with her mother.

While at an out-of-town forensic pathology convention, Rosewood unintentionally reveals the blueprint to commit the perfect murder during a speech to the convention attendees. Tormented, and armed only with a hunch, Rosewood enlists Villa to help solve the crime, and while investigating undercover, sparks fly unexpectedly between them. Hornstock and Floyd Butters are called upon for extra help. Meanwhile, Pippy and TMI have locked themselves in the lab overnight to help with the investigation and TMI receives an unexpected visit from her estranged father.

An old flame of Rosewood's shakes up Rosewood's life when she returns to enlist his help in finding a wealthy patient of hers who's disappeared. But when the man's body surfaces, triggering a murder investigation, things are not what they appear to be. As the bizarre turns of this case come to a head, so does Rosewood's personal life as he is pushed to make decisions regarding all the women in his world.

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A hostage situation erupts at the East Miami Police Department, and Rosewood, Villa and Slade are trapped on the inside. Rosewood forms a strong bond with their captor and must solve his biggest medical mystery to date in order to keep his team alive.

Rosewood and Villa are pulled into the world of human trafficking to investigate the death of a school teacher, and a surprising insight into Slade's past draws Rosie and Villa closer than ever before.