Introduction Medical students report poor academic well-being in a context of high study demands. Study Demands–Resources theories have outlined mediating processes involving high study demands and low resources to mitigate academic well-being, which is subsequently associated with diminished overall well-being (i.e. life satisfaction). Furthermore, academic well-being and life satisfaction are also affected by interactions between study demands and resources (referred to as moderating processes). However, these mediating and moderating processes clarifying medical students' well-being still need to be investigated. Therefore, this study investigated the mediating role of academic well-being in the associations of study demands and resources with life satisfaction and the moderating role of study demands and resources in relation to academic well-being and life satisfaction among undergraduate medical students. Methods In this cross-sectional survey study, 372 undergraduates from Dutch medical schools participated. The survey included the Study Demands–Resources Scale (workload, growth opportunities and peer support) as well as questionnaires on academic well-being (Utrecht Burnout Scale for students and Utrecht Work Engagement Scale-Student Form) and overall well-being (single item on life satisfaction). Based on Study Demands–Resources theories, (moderated) mediation analyses were performed. Results Mediating processes were found as growth opportunities were indirectly associated with higher life satisfaction through lower academic burnout and higher academic engagement. Furthermore, workload was indirectly associated with lower life satisfaction through higher academic burnout. This association was moderated as it became weaker with more perceived peer support. Discussion A high workload and limited growth opportunities are associated with suboptimal academic well-being and life satisfaction. Perceiving support from peer students slightly buffers the unfavourable effect of workload on academic burnout and ...