Atelier Ayesha: The Alchemist of Dusk is the fourteenth installment in the Japanese Atelier series. The game follows Ayesha, a lonely girl who makes and sells medicine to a traveling merchant. She lives alone in an herbalist's workshop after the presumed death of her sister, Nio. During a visit to her grave, Ayesha witnesses a vision of her sister. She is then told by a traveling alchemist that her sister is in fact not dead, just "missing". The story follows Ayesha and her quest to find her missing sister.
The gameplay is divided into two core segments: Combat and Synthesis. Combat is conducted in a turn-based manner, allowing players to strategically position their characters to deal more damage or provide extra support to teammates. Super moves are also reintroduced, where characters unleash devastating attacks conducted through a cinematic. Synthesis involves gathering supplies and using your alchemy to create items for quests, combat, or health regeneration. Higher quality item yield results in better quest material, damage, and regeneration.
The game features a time management system, requiring players to complete the game within 3 years of in-game time. Completing the game on time rewards one of the 10 possible endings, while missing the deadline results in an alternate conclusion.