Human activities have significantly altered atmospheric composition, leading to severe air pollution with profound consequences for public health and ecosystem integrity. This study presents a comprehensive assessment of the integrated health and ecological impacts caused by anthropogenic emissions across 41 prefecture-level cities in the Yangtze River Delta (YRD) region of China. By coupling response surface modeling with monetization methods, we quantify the local and intercity impacts of PM2.5- and O3-related health burdens, nitrogen deposition-induced ecological damage, and crop losses. Results show that an estimated total economic loss of CNY 2630.5 billion was attributed to anthropogenic emissions in 2020, equivalent to 11% of the regional GDP. PM2.5-related health damage was the largest contributor, accounting for 59.2% of total losses, followed by nitrogen deposition-driven ecological damage (32%). Regional pollution was found to be the dominant pathway for pollution-induced damages, contributing 91% more than local emissions. Suzhou(Jiangsu) and Shanghai were identified as key source prefecture-level cities, while agriculture, industrial processes, and on-road vehicles are priority sectors for tailored emission control to effectively reduce integrated economic damages. This study highlights the importance of integrating health and ecological effects in policy design and emphasizes the need for coordinated, cross-boundary pollution management strategies. These findings provide scientific support for developing integrated, multipollutant control measures to promote sustainable urban and regional development in rapidly industrializing regions like the YRD region.