Qualitative comparative analysis (QCA) is a hybrid method designed to bridge the gap between qualitative and quantitative research in a case-sensitive approach that considers each case holistically as a complex configuration of conditions and outcomes. QCA allows for multiple conjunctural causation, implying that it is often a combination of conditions that produces an outcome, that multiple pathways may lead to the same outcome, and that in different contexts, the same condition may have a different impact on the outcome. This approach to complexity allows QCA to provide a practical understanding for complex, real-world situations, and the context of implementing interventions. There are guides for conducting QCA in primary research and quantitative systematic reviews yet, to our knowledge, no guidance for conducting QCA in systematic mixed studies reviews (SMSRs). Thus, the specific objectives of this paper are to (1) describe a step-by-step approach for novice researchers for using QCA to integrate qualitative and quantitative evidence, including guidance on how to use software; (2) highlight specific challenges; (3) propose potential solutions from a worked example; and (4) provide recommendations for reporting.