Objectives: Whole-school interventions and programmes aim to change school environments to promote health. Previous reviews suggest these are often inappropriately informed by individualistic psychological theories. We undertook a systematic review of whole-school interventions to prevent substance use and violence. This paper reports on a synthesis of theories of change, assessing whether these aligned with, and suggested refinements to, the theory of human functioning and school organisation, a more encompassing, sociological theory. This theory proposes that schools improve health by promoting student commitment, achieved by eroding various ‘boundaries’ (e.g. between staff and students) and reframing provision based on student needs so that students commit more fully to school ‘instructional’ (learning) and ‘regulatory’ (behaviour) orders. Setting: International. Design: Systematic review. Methods: The study involved systematic searches, data extraction and quality assessment. Theories of change were synthesised using a best-fit framework. Results: Despite only one intervention being explicitly informed by the theory of human functioning and school organisation, the theories of change of most interventions aligned (at least in part) with aspects of this theory. Synthesis suggested various refinements to the theory. First, it suggested specific activities that can modify boundaries and reframing to increase student commitment. Second, it refined the concept of reframing to include building learning on existing student knowledge using a ‘constructivist’ approach. Third, it suggested future intervention might usefully seek to erode boundaries between the ‘instructional’ and ‘regulatory’ orders of the school to create a single ‘developmental’ order. Finally, it recognised that whole-school interventions might prevent violence and substance use among students in ways other than by building student commitment. Conclusion: Our refined theory of change provides a firmer basis for interventions. Future work is needed to examine empirical support for the refined theory.