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Climate change is reshaping indoor-outdoor pollution dynamics, yet current building standards rarely reflect this shift. In rapidly urbanizing regions with high ambient PM_2.5 levels, building airtightness offers an underutilized strategy to mitigate indoor exposure and associated health burdens. An analysis of 36 major Chinese cities across five climate zones shows that improving building airtightness lowers indoor PM_2.5 and reduces COPD-related mortality. We identify an airtightness effectiveness transition zone that broadly aligns with the summer monsoon boundary, where weakened summer pressure gradients can offset up to half of the expected infiltration gains. At best practice levels, indoor PM_2.5 declines by 10.6 % and COPD deaths by 6.2 %, with the largest benefits in cold regions. Western cities display disproportionately high COPD mortality despite lower exposures, highlighting structural inequities in vulnerability. These results support climate-specific airtightness targets paired with ventilation and filtration, retrofit prioritisation for leaky and vulnerable housing, and the use of joint energy health metrics to guide funding, offering a potentially scalable pathway to healthier and more energy-efficient buildings in rapidly urbanizing regions.