In the city of Salburg, there has always been a long tradition of alchemy - a magical science that dealt with combining various materials and turning metals into gold. Two young girls, Marlone and Elvira, have to study at the Academy of Alchemy, make powerful items, and prove to their masters they are worthy to be real alchemists.

Futari no Atelier is a Japanese-style role-playing game with light simulation elements. The heroines have to read books and talk to people in order to learn more about items, and then buy these items or find them somewhere. They must then combine powerful items in order to impress their teachers. The player also develops the characters in a standard RPG fashion. They can equip weapons and armor, and fight random enemies in wilderness areas. The characters gain levels and become stronger the more enemies they fight. The battles are automatic, and it is only possible to assign a general strategy to the characters.