Following the conclusion of Professor Layton and the Miracle Mask, the Azran Legacies, the relic of an ancient civilization, are now possessed by a mysterious organisation named Targent, who wish to utilise the Azrans' power for themselves. In addition, Jean Descole, Targent's rival, also wishes to utilise the Azran Legacies, thus setting the stage as the conflict for the Legacies unfolds.

The story follows Professor Hershel Layton, his assistant Emmy Altava, and his apprentice Luke Triton as they travel to the snowladen city of Snowrassa to investigate a ‘living mummy’. There, they find a girl named Aria, who comes from an ancient race known as the Azrans, frozen in ice. After freeing her and realizing she has lost her memory, their investigation takes them around the world