We propose a conceptual framework which may guide research on fostering diagnostic competences in simulations in higher education. We first review and link research perspectives on the components and the development of diagnostic competences, taken from medical and teacher education. Applying conceptual knowledge in diagnostic activities is considered necessary for developing diagnostic competences in both fields. Simulations are considered promising in providing opportunities for knowledge application when real experience is overwhelming or not feasible for ethical, organizational or economic reasons. To help learners benefit from simulations, we then propose a systematic investigation of different types of instructional support in such simulations. We particularly focus on different forms of scaffolding during problem-solving and on the possibly complementary roles of the direct presentation of information in these kinds of environments. Two sets of possibly moderating factors, individual learning prerequisites (such as executive functions) or epistemic emotions and contextual factors (such as the nature of the diagnostic situation or the domain) are viewed as groups of potential moderators of the instructional effects. Finally, we outline an interdisciplinary research agenda concerning the instructional design of simulations for advancing diagnostic competences in medical and teacher education.