ObjectivesThere is a need for novel approaches to address the complexity of social inequality in health. Public–private partnerships (PPPs) have been proposed as a promising approach; however, knowledge on lessons learnt from such partnerships remain unclear. This study synthesises evidence on opportunities and challenges of PPPs focusing on social inequality in health in upper-middle-income and high-income countries.DesignA systematic literature review and meta-synthesis was conducted using the Mixed Methods Appraisal Tool for quality appraisal.Data sourcesPubMed, PsychInfo, Embase, Sociological Abstracts and SocIndex were searched for studies published between January 2013 and January 2023.Eligibility criteriaStudies were eligible if they applied a quantitative, qualitative, or mixed methods design and reported on lessons learnt from PPPs focusing on social inequality in health in upper-middle-income and high-income countries. Studies had to be published in either English, Danish, German, Norwegian or Swedish.Data extraction and synthesisTwo independent reviewers extracted data and appraised the quality of the included studies. A meta-synthesis with a descriptive intent was conducted and data were grouped into opportunities and challenges.ResultsA total of 16 studies of varying methodological quality were included. Opportunities covered three themes: (1) creating synergies, (2) clear communication and coordination, and (3) trust to sustain partnerships. Challenges were identified as reflected in the following three themes: (1) scarce resources, (2) inadequate communication and coordination, and (3) concerns on distrust and conflicting interest.ConclusionsPartnerships across public, private and academic institutions hold the potential to address social inequality in health. Nevertheless, a variety of important lessons learnt are identified in the scientific literature. For future PPPs to be successful, partners should be aware of the availability of resources, provide clear communication and coordination, and address concerns on distrust and conflicting interests among partners.PROSPERO registration numberCRD42023384608.