Reported burnout rates among qualified healthcare professionals (QHP) are alarming. Systematic reviews evaluating the effectiveness of burnout interventions for QHP exist; however, findings are contradictory. In addition, to date, there is no indication of how these interventions work and what specific intervention elements mitigate burnout. This review aims to explain how burnout interventions work and the contextual factors that mediate the intended outcomes. Our ultimate goal is to formulate actionable recommendations to guide the implementation of complex burnout interventions for QHP working in the hospital setting. In light of the heterogeneity and complexity of the interventions designed to address burnout, we will conduct a realist review using Pawson's five iterative stages to explore and explain how burnout interventions work, for whom, and in what circumstances. We will search PubMed, CINAHL, Scopus, PsycINFO and Web of Science from inception to December 2022. Grey literature sources will also be considered. The results will be reported according to the Realist and Meta-Narrative Evidence Syntheses-Evolving Standards quality and publication standards ETHICS AND DISSEMINATION: Findings will be disseminated in a peer-reviewed journal, conference presentations and through the development of infographics and relevant educational material to be shared with stakeholders and key institutions. This study is a secondary data analysis; thus, a formal ethics review is not applicable. CRD42021293154.