Serious games, as a learning resource, enhance their game character by embedding game design elements that are typically used in entertainment games. Serious games in its entirety have already proven their teaching effectiveness in different educational contexts including medical education. The embedded game design elements play an essential role for a game's effectiveness and thus they should be selected based on evidence-based theories. For game design elements embedded in serious games used for the education of medical and healthcare professions, an overview of theories for the selection lacks. Additionally, it is still unclear whether and how single game design elements affect the learning effectiveness. Therefore, the main aim of this systematic review is threefold. Firstly, light will be shed on the single game design elements used in serious games in this area. Second, the game design elements' underlying theories will be worked out, and third, the game design elements' effectiveness on student learning outcome will be assessed. Two literature searches were conducted in November 2021 and May 2022 in six literature databases with keywords covering the fields of educational game design, serious game, and medical education. Out of 1006 initial records, 91 were included after applying predefined exclusion criteria. Data analysis revealed that the three most common game design elements were points, storyline, and feedback. Only four underlying theories were mentioned, and no study evaluated specific game design elements. Since game design elements should be based on theories to ensure meaningful evaluations, the conceptual GATE framework is introduced, which facilitates the selection of evidence-based game design elements for serious games.