Robert Langdon, a renowned symbologist, wakes up in a hospital in Florence, Italy, with no memory of how he got there. Suffering from amnesia and haunted by cryptic visions and a nightmarish puzzle related to Dante Alighieri's "Inferno," he finds himself on the run with Dr. Sienna Brooks, a young doctor who helps him escape after they are attacked by a mysterious assailant. Langdon discovers that he is in possession of a high-tech biohazard container containing a projector that displays a modified map of Dante's Inferno, thrusting them into a globe-trotting race against time.

As Langdon and Sienna unravel the enigmatic clues, they realize that a billionaire geneticist named Bertrand Zobrist, who was obsessed with Dante's work and recently committed suicide, might have left behind a deadly virus with the potential to decimate half of the world's population. With the help of Langdon's extensive knowledge of symbols and Dante's literature, they navigate the hidden passages of Florence, decode cryptic messages, and seek the truth behind Zobrist's disturbing Inferno while pursued by both law enforcement and covert agents with their own agendas.