The game features an original story by Hiromu Arakawa from the creator of the Fullmetal Alchemist manga.
Taking place between episodes 17 and 18 of the anime, the game begins with the Elric brothers (somewhat unwillingly being escorted by Major Alex Louis Armstrong) heading to Central City via train. While Ed moans, Al consoles, and Armstrong flexes, the train is suddenly attacked by terrorists. The skirmish eventually ends with one destroyed train and the brothers in the town of New Heissgart, looking for a ride to Central. There, they meet a girl named Armony and learn more of the Philosopher's Catalyst, an item nearly as powerful as the Philosopher's Stone itself, but used to increase the efficiency of alchemy. The Philosopher's Catalyst seems to be directly linked with the berserk chimeras running about, the rogue military force, and the gathering of alchemists in the town. The Elrics soon find that their simple mission for a train turns into much more as they learn about the Catalyst and the dark mysteries surrounding it.