Background: The commercial determinants of health (CDoH) drive the rise of NCDs globally, and their regulation requires multisectoral governance. Despite existing recommendations to strengthen institutional structures, protecting public health interests can be challenging amidst industry interference and conflicting policy priorities, particularly in low and middle-income countries (LMICs) where the need for rapid economic development is pronounced. Small island developing states (SIDS) face even more challenges in regulating CDoH because their unique socioeconomic, political, and geographic vulnerabilities may weaken institutional conditions that could aid health sector actors in protecting health interests. This study aims to explore the institutional conditions that shape health sector actors’ capability to protect public health interests in tobacco governance in Fiji and Vanuatu. Methods: We employed a qualitative, exploratory case study design. We applied the administrative process theory to inform data collection and analysis. Seventy interviews were completed in Fiji and Vanuatu from 2018 to 2019. Results: The findings show that the protection of health interests in tobacco governance were not supported by the institutional conditions in Fiji and Vanuatu. While the policy processes formally ensured a level playing field between actors, policies were often developed through informal mechanisms, and the safeguards to protect public interests from vested private interests were not implemented adequately. SIDS vulnerabilities and weak regulation of political parties contributed to the politicisation of government in both states, resulting in high-level government officials’ questionable commitment to protect public health interests. The system of checks and balances usually embedded into democratic governments appeared to be muted, and policymakers had limited bureaucratic autonomy to elevate health interests in multisectoral policymaking amidst high-level government officials’ frequent rotation. Finally, capacity constraints aggravated by SIDS vulnerabilities negatively impacted health sector actors' capability to analyse policy alternatives. Conclusions: Health sector actors in Fiji and Vanuatu were not supported by institutional conditions that could help them protect public health interests in multisectoral governance to regulate CDoH originating from the tobacco industry. Institutional conditions in these states were shaped by SIDS vulnerabilities but could be improved by targeted capacity building, governance and political system strengthening.