Atelier Ayesha: The Alchemist of Dusk is the fourteenth installment in the Japanese Atelier series. The game follows Ayesha, a girl who makes and sells medicine to a merchant. She lives alone in an herbalist's workshop after her sister's presumed death. During a visit to her grave, Ayesha sees a vision of her sister. She is then told by an alchemist that her sister is not dead, but missing. The story follows Ayesha as she searches for her missing sister.
The gameplay is divided into two main parts: Combat and Synthesis. Combat is turn-based, with players able to position their characters to deal more damage or provide support to teammates. Super moves are also back, allowing characters to unleash powerful attacks in a cinematic sequence. Synthesis involves gathering supplies and using alchemy to create items for quests, combat, or health regeneration. The quality of the items affects the results, with higher quality yielding better outcomes.
The game features a time management system, where players have three years to complete the game. If not completed on time, one of ten different endings is unlocked.