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The ecological environment of the remote plateaus has been a challenge plaguing many countries due to global warming, increased human activities, and frequent occurrence of various heavy metal (HM) pollutants. This paper analyzes the primary factors and potential susceptible regions’ characteristics related to soil HMs (As, Cd, Pb, Cr, Ni, and Zn) in the southern Tibet Plateau (TP) using Geo-detectors and a set of multi-source data from remote sensing and geographic and geological information. The geoaccumulation index showed that the As pollution was the most serious. The precipitation, pH, geological age (GA), and rock type (RT) were the most critical factors affecting HMs. Additionally, soil HMs were relatively unaffected by land use and clay. Based on the risk detector, the most key impact types (range) of the predominant factors of HM’s sources were identified. For example, precipitation (100–200 mm), pH (7–7.5), DEM (>5500 m), RT (ophiolite), and GA (Ordovician) had the highest average concentration of As in each type (ranges) of the predominant factors. This work provides new data on the extent of soil HM contamination in the southern TP and predicts vulnerable areas of HM contamination, providing an important scientific basis for monitoring and managing HM in remote areas at high altitudes.