PM2.5 pollution is becoming increasingly severe in Southeast Asia (SEA) due to its health and ecosystem impacts. To effectively evaluate health impacts and provide a scientific foundation for developing national and regional strategies to enhance air quality, a comprehensive understanding of the chemical composition of PM2.5 is essential, with particular attention to toxic and persistent compounds (e.g., Per – and Polyfluoroalkyl Substances (PFAS) and mercury (Hg)). PFAS and Hg are two hazardous pollutants with distinct characteristics, yet both have the potential to cause dangerous risks to human health and the environment. PFAS are highly persistent and bioaccumulative, while Hg can bioaccumulate and cause harm within the food chain. Our project aims to investigate the levels and fate of PFAS and Hg in PM2.5 in big cities across SEA and Japan. PM2.5 samples will be collected from urban cities in 4 countries (Vietnam, Malaysia, Indonesia, and Japan). We will conduct a cross-country analysis to compare PFAS and Hg levels and evaluate their impact on health and environmental sustainability. The project outcomes are expected to provide evidence-based policy recommendations for stakeholders, including local governments and environmental management agencies, to develop pollution prevention strategies for PFAS and Hg contamination. In addition, our project could also create reliable methods for PFAS and Hg analysis that can be widely used in the region.