Background <p>Most climate and health studies are based on a single extreme weather event and do not consider multiple physical processes across spatial and temporal scales. Our aim was to explore the current landscape of epidemiologic evidence on health effects linked to compound climate extreme events, compared with individual climate extreme events. We placed particular attention on exposure characterization methods and identifying opportunities for future research.</p> Methods <p>We searched the Web of Science, Scopus, and Medline/OVID databases for original research articles, using key concepts related to compound climate events, extreme events, and health risks between January 1950 and November 2025. Three reviewers conducted title/abstract screening and double-reviewed the remaining articles. We also developed a conceptual framework to outline the pathways between compound climate extremes and health outcomes.</p> Results <p>Our review identified 37 studies exploring the health impacts of compound climate events. The health outcomes assessed were mortality, mental health, cardiovascular, respiratory, adverse pregnancy, and others. Most study designs were time-series or case-crossover, and several studies identified vulnerable subpopulations. Most quantitative studies reveal that compound climate extreme events exhibit an elevated risk of health impacts (<i>n</i> = 34), especially compared to non-compound events (<i>n</i> = 31). Among the 27 studies that compared health risks of compound extremes with their individual component events, 20 found an elevated risk of the compound event. Only seven studies assessed synergistic effects formally, with four indicating a greater joint risk of compound climate events compared to what would be expected from the combined effects of those events in isolation.</p> Conclusions <p>There is an emerging body of literature characterizing the substantial health impacts of compound climate extremes. Research has increasingly explored spatial heterogeneity and complex exposure–response associations emerging from compound climate exposures; however, definitions used to characterize compound climate extremes vary widely. Future research should further examine the synergistic mechanisms of compound climate extreme events and determinants of associated health outcomes to enhance public health and disaster preparedness, using a flexible exposure definition framework.</p>