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Myanmar has undergone a remarkable political transformation in the last 2 years, with its leadership voluntarily transitioning from an isolated military regime to a quasi-civilian government intent on re-engaging with the international community. Decades of underinvestment have left the country underdeveloped with a fragile health system and poor health outcomes. International aid agencies have found engagement with the Myanmar government difficult but this is changing rapidly and it is opportune to consider how Myanmar can engage with the global health system strengthening (HSS) agenda. Nineteen semi-structured, face-to-face interviews were conducted with representatives from international agencies working in Myanmar to capture their perspectives on HSS following political reform. They explored their perceptions of HSS and the opportunities for implementation. Participants reported challenges in engaging with government, reflecting the disharmony between actors, economic sanctions and barriers to service delivery due to health system weaknesses and bureaucracy. Weaknesses included human resources, data and medical products/infrastructure and logistical challenges. Agencies had mixed views of health system finance and governance, identifying problems and also some positive aspects. There is little consensus on how HSS should be approached in Myanmar, but much interest in collaborating to achieve it. Despite myriad challenges and concerns, participants were generally positive about the recent political changes, and remain optimistic as they engage in HSS activities with the government.