BACKGROUND: Within increasingly constrained school timetables, interventions that integrate academic and health education to reduce substance use and violence may hold promise as a category of intervention that can positively affect both academic and health outcomes. There are no current systematic reviews exploring the effectiveness of such interventions or factors that affect their implementation. METHODS: A total of 19 bibliographic databases and 32 websites were searched. References were also extracted from the reference lists of included studies, and experts and authors were contacted to identify relevant studies. We included reports with no restrictions on language or date. References were screened on title/abstract and those not thus excluded were screened on full report. Data extraction and appraisal followed the Critical Appraisal Skills Programme, Evidence for Policy and Practice Information and Co-ordinating Centre and Cochrane tools. Extracted process data were qualitatively meta-synthesised for common themes. RESULTS: Seventy-eight thousand four hundred fifty-one unique references were identified, and 62 reports were included. A total of 16 reports (reporting on 15 studies of 12 interventions) evaluated process. Key facilitators of integrated academic and health curricula were supportive senior management and alignment of the intervention with school ethos; a positive teaching environment, including positive perceptions around the ability to be flexible in the adaptation and delivery of integrated academic and health curricula; positive pre-existing student and teacher attitudes towards intervention content; and parental support of interventions, largely through reinforcement of messaging at home. Important barriers were over-burdened teachers, with little time to learn and implement integrated curricula. CONCLUSION: Several useful facilitating and inhibiting factors linked to the implementation of interventions that integrate academic and health education for reduced substance use and/or violence were identified, providing tentative but insightful evidence of context-specific issues that may impact intervention success. However, overall, there is still a considerable gap in our understanding of how to achieve the successful implementation of these interventions.