Set against the vibrant backdrop of one of the world's hottest cities - Miami - private pathologist Dr. Beaumont Rosewood, Jr. must crack a case that hits close to home. As he begins his investigation, Detective Annalise Villa gives him a run for his money as they cross paths and are forced to work together to help the Miami PD solve the case.

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.

Rosewood’s partnership with Villa faces an uncertain future when she’s paired with a recent transfer to the East Miami PD, with whom she shares a past. As Villa and her new partner investigate the death of a suburban dentist who ran a yuppie drug ring, Rosewood can’t shake the feeling that his “replacement” knows more about the victim’s narcotics business than he’s letting on. Meanwhile, a new medical examiner, Dr. Anita Eubanks, is brought in to help with the investigation and Hornstock’s insecurities hinder his ability to handle the public relations side of the case, forcing him to turn to an unlikely source for help

Rosie insists on celebrating his and Villa's nine-and-a-half month anniversary as partners, which lands them in the middle of a case involving none other than Julius "Joo-Joo" Beeman, their confidential informant. But, this time, Joo-Joo is the prime suspect. As Rosie and Villa work to uncover the truth, even if it means putting Joo-Joo away for life, they discover a whole new side of him they never saw coming. Meanwhile, Villa's choice for her new home has Rosie worried about the new path she's on, Pippy and TMI struggle to balance old friends and family, and Hornstock has trouble reading signals from the new, badass, female chief of police.

The investigation into Gerald's case leads Rosewood and Villa to Cuba, where they confront two new mysteries; TMI brings her former roommate to help decipher evidence.