Set in 1896, following the events of The Testament of Sherlock Holmes, after Professor James Moriarty's death, Sherlock Holmes is now taking care of Moriarty's daughter, Katelyn, while keeping her true origin as a secret. However, the situation changes when a mysterious woman known as "Alice" becomes Holmes's new neighbor. Alice slowly befriends Katelyn, eventually earning the daughter's trust while causing emotional issues between Holmes and Katelyn at the same time. Throughout the game, Holmes will solve different cases while getting to know Alice's origin and her true intention.
Once discovered, clues are added to a "deduction board", a gameplay mechanic which involves linking pieces of information together, leading to possibilities for different deductions. Once deductions are connected together, the player will have a full tree of deductions in the player's memory called mind palace. Depending on how players interpret the clues, they will arrive at different conclusions. Thus, the player can fail or succeed in finding the culprit.