The Sorceress tells the tale of Nicholas Flamel and the twins and their adventures and hardships as they attempt to rescue Nicholas' wife Perenelle, the Sorceress, from Alcatraz. The story is similar to many folktales, since it explains various phenomena and creatures of myth. In the end the Sorceress rescues herself and meets this trio. The entire story takes place in a matter of only two days.

The story follows the lives of various humani, immortals, and other creatures of folklore in modern times as they fight to have control over the future of the world. This story is the sequel to a series of books about Nicholas Flamel. The Dark Elders and their immortal humani followers, such as Dr. John Dee and Niccolo Machiavelli, want to bring back the Dark Elders from the various Shadowrealms into which they have been cast. This would most likely lead to the end of humanity. The Flamels and their allies wish to keep the Dark Elders trapped in the Shadowrealms to protect the world from their power. There are also various characters who share beliefs and allegiances with both sides.

To successfully take control of the world, the Book of Abraham and the twins of legend must be in one's possession. During this book, the twins and the last two pages of the Book of Abraham, the Codex, are in the hands of the Flamels, while Dee and his allies have the rest of the book. What would aid Dee and others like him would be Perenelle's death. She is very powerful, and if she were not alive, they would stand a better chance of catching the twins, completing the Book of Abraham, and taking over the world. Machiavelli spends much of the story underestimating Perenelle's skills and intelligence, while Dee ends up hiding from his master Elder because he is unable to capture Nicholas.

The plot of this book takes the reader on various adventures in London, Paris, and San Francisco as NIcholas and his allies try to get to Perenelle and their enemies attempt to capture and/or kill them. The book ends with many questions left unanswered. Although the Flamels are reunited and the twins are safe with them, Dee is still alive, and it is only a matter of time before trouble finds the Flamels, the twins, and their allies.