While working at pleasant but mundane summer jobs in San Francisco, fifteen-year-old twins, Sophie and Josh, suddenly find themselves caught up in the deadly, centuries-old struggle between rival alchemists, Nicholas Flamel and John Dee, over the possession of an ancient and powerful book holding the secret formulas for alchemy and everlasting life.

While armies of the Shadowrealms gather and Machiavelli goes to Alcatraz to kill Perenelle Flamel, fifteen-year-old twins Sophie and Josh Newman accompany the Alchemist to England to seek Gilgamesh.

Fifteen-year-old Josh has chosen to side neither with his twin sister Sophie nor with the Alchemyst, Nicholas Flamel, but rather to fight alongside Dr. John Dee and the mysterious Virginia Dare, while the immortal Machiavelli and Billy the Kid follow the Elders' plans to set loose the monsters of Alcatraz on San Francisco and trigger the end of the human race.