China's rapid economic growth and social transitions have deteriorated environmental conditions and caused further public health issues in last three decades. This study examines the complex mechanisms of how socioeconomic transitions and physical environmental conditions impact public health, especially with respect to increasing cancer incidences in mainland China from a spatial-temporal perspective. Specifically, (1) spatial variations of seven types of cancer incidences were analyzed in relation to heavy metal emissions from industrial wastewater at the prefecture-level city scale from 2004 to 2009. Additionally; (2) spatial statistical methods were employed to explore the associations between health outcome, heavy metal emissions from industrial wastewater (arsenic, chromium, cadmium, mercury, lead), as well as socioeconomic transitions (industrialization, urbanization, globalization) and physical environmental factors (hydrology and vegetation coverage). Results showed a significant increase of cancer incidences between 2004 and 2009. Consistent with the spatial pattern of heavy metal emissions, cancer patient clusters were identified in both traditional industrial bases and newly industrialized economic zones, especially in major cities located at downstream watersheds, including Beijing, Shanghai, Guangzhou, Shenyang, and Wuhan. The results also revealed the double-edged effects of industrialization, economic growth, and urbanization on natural environment and human health. The findings provide informative knowledge of heavy metal pollution and cancer outbreaks in China and therefore offer valuable reference for authorities formulating regulations.