BACKGROUND: While there is a growing body of legally-focused analyses exploring the potential restrictions on public health policy space due to international trade rules, few studies have adopted a more politically-informed approach. This paper applies an integrated political economy and power analysis approach to understand how power relations and dynamics emerging as a result of the international trade and investment regime influence nutrition and alcohol regulatory development in a case study of South Africa. METHODS: We interviewed 36 key stakeholders involved in nutrition, alcohol and/or trade/investment policymaking in South Africa. Interview transcripts and notes were imported into NVivo and analyzed using thematic analysis. We used a conceptual framework for analyzing power in health policymaking to guide the analysis. RESULTS: Under the neoliberal paradigm that promotes trade liberalization and market extension, corporate power in nutrition and alcohol policymaking has been entrenched in South Africa via various mechanisms. These include via close relationships between economic policymakers and industry; institutional structures that codify industry involvement in all policy development but restrict health input in economic and trade policy decisions; limited stakeholder knowledge of the broader linkages between trade/investment and food/alcohol environments; high evidentiary requirements to prove public health policy effectiveness; both deliberate use of neoliberal frames/narratives as well as processes of socialization and internalization of neoliberal ideas/values shaping perceptions and policy preferences and ultimately generating policy norms prioritizing economic/trade over health objectives. CONCLUSIONS: Exposing power in policymaking can expand our own ideational boundaries of what is required to promote transformative policy change. This work points to a number of potential strategies for challenging corporate power in nutrition and alcohol policymaking in the context of international trade and investment liberalization in South Africa.