British Museum curator Lady Alex Lindo-Parker travels to the Amazon in search of the lost camp of Victorian explorer Percy Fawcett. A series of mishaps sees her joined by maverick American adventurer Hooten and they stumble upon El Dorado.
Hooten asks Lady Alex to help him find the long lost Sibylline Books, a collection of mystical prophecies. In Rome, the museum curator quickly finds herself scaling the Sistine Chapel, battling a sewer alligator and facing the Mafia.
When Alex travels to Egypt she once again teams up with Hooten, this time to try and find the long-lost tomb of Alexander the Great - but the intrepid pair soon discover that some unscrupulous locals are on their trail.
Alex gets a lead on an ancient scroll that is rumoured to have been written by the Buddha himself. She enlists Hooten to go with her to the Himalayan kingdom of Bhutan to find it but ends up racing against time to save his life.
When Ella is kidnapped in Ethiopia, Alex borrows a priceless artefact from the British Museum for the ransom and begs Hooten for help. The pair must overcome stubborn camels and crazed bandits to decode a mystery of biblical proportions.
Alex goes to Moscow to aid Hooten in his search for a lost Fabergé egg and confronts her arch-enemy from University, who now works for a black market collector. Hooten meets his master thief mentor who sends the pair on a perilous journey.