The story follows twelve-year-old Amy Cahill and her younger brother Dan as they compete against other branches of their wealthy family to find thirty-nine clues that will lead to a powerful fortune and the secret of their family's past. The first clue leads them to a hidden tomb in Paris beneath the Eiffel Tower. There they find a small brass cylinder containing a coded message that leads them on their quest.
Along the way, they meet several allies, including Jonah Wizard, a genius with a photographic memory; Nellie Gomez, a resourceful street urchin who helps them in Paris; and Alistair Oh, a martial arts expert who becomes their bodyguard. They must also face off against several villains, including the Cabras, a ruthless branch of the Cahill family, and the Lucian, a powerful secret society that wants to keep the Cahills from winning the clues.
The novel ends with the Cahills finding out that their grandmother Grace Cahill is still alive and a part of the Lucian.
The Maze of Bones was critically acclaimed and was praised for its fast-paced action, suspense, and plot. It was also commercially successful, debuting at number one on The New York Times Best Sellers list.