Due to high geological background and intensive mining activities, soils are prone to heavy metals (HMs) accumulation and ecological fragility in Guizhou Province, China. A total of 740 topsoil samples were therefore collected, and aimed to determine the concentrations of As, Cd, Cr, Hg, and Pb, estimate the ecological pollution, and evaluate the carcinogenic and non-carcinogenic health risks to humans. Results showed As (1.08%) and Cd (24.46%) in soil exceeded standards. The Igeo showed that Cr (1.49%) and Hg (31.62%) in soil were at light pollution levels; single factor pollution index (PI) showed that Cd (21.35%) in soil was mildly polluted; risk index (RI) as at a low risk level. Notably, both deterministic and Monte Carlo analyses revealed unacceptable carcinogenic risks for As and Cr in children, with traditional methods potentially underestimating As risks. Moreover, Target-Organ Toxicity Dose (TTD) revealed soil HMs as a higher risk to hematological health, with notable health risks posed by Pb in children. It is noted that spatial distribution analysis suggested that the southwestern region of Guizhou Province should be prioritized for health risk management and control. By integrating the uniqueness of geological environments, multi-dimensional health risk assessments, and spatial distributions, the present study provides a scientific basis for assessing HMs pollution risks and soil health risks in the karst regions.