At the start of the game, players are given a choice between two characters: Razeluxe Meitzen (or Raze for short) or Ulrika Mulberry. The events that plays out following the choice of characters differs greatly as Raze's route deals with his past while Ulrika's route deals with the origin of Mana. But in either character's playthrough, the core events will still remain the same (taking alchemy classes and school events), though the jobs available may slightly differ.

The game prologue describes Al-Revis Academy (アルレビス学園 Aru-Rebisu Gakuen), a famous alchemy school which used to be floating, separated from the Lower World (where ordinary humans live). But due to the weakening power of Mana which kept the school afloat, Al-Revis Academy plummets down to the Lower World. It soon manages to adapt to the surroundings with the help of students and teachers and resumes its activities in teaching alchemy.

But due to the school's dwindling budget, they have to search for sponsors to keep the school running and Marta Schevesti was given the position of 'Chairman' (理事長 rijichou) of the school due to her being the spokesperson of the sponsors. She proposed to start a new class; 'Combat Class' (戦闘技術 sentou gijitsu) so that more students will enroll in the school to boost the school's finance. But her main goal is to remove alchemy from the school's syllabus stating that "it's a waste of money" (a rough translation).

Al-Revis Academy's principal, Zeppel (of the previous game), was a little too weak-willed to stop her and he seeks Flay (also from the first Mana Khemia) to help and appoints Flay as the classroom teacher for the new class, which Raze and Etward enroll in. Tony (the third recurring character from the previous game) is the homeroom teacher for the alchemy class, with Ulrika, Chloe and Lily under him.

Mana Khemia 2: Fall of Alchemy screenshots