From the moment Otis and Cody Carson arrive on Skull Island to stay at their aunt's inn, they know something is wrong. A giant snake turns up on their aunt's bed, one of the rooms is violently ransacked, and then a celebrity guest goes missing. Could a ghost be responsible—or pirates?

Otis, Cody, and Rae are thrilled to fly down to the Amazon, where the twins' dad has a commission to paint a portrait of coffee baron Enrico Estevez. But then a speeding car tries to run down Mr. Estevez and an overnight in the jungle turns terrifying when the kids encounter deadly animals...and even deadlier smugglers.