The leachability of heavy metals (HMs) in tailings is significantly affected by multivariate factors associated with environmental conditions. However, the leaching patterns of HMs in molybdenum (Mo) tailings due to environmental change and cumulative influences of multi-leaching factors remain unclear. The leaching behaviors of HMs in Mo tailings were studied through static leaching tests. The key leaching factors were discussed via simulating acid rain leaching scenario in terms of global and local environmental conditions. The potential risk factors were identified, and their cumulative influences on the leachability of HMs were evaluated with boosted regression trees (BRT) and generalized additive model (GAM) analyses. Environmental factors showed interactive effects on the leachability of HMs in tailings. The leachability of HMs in tailings decreased significantly with the interaction of increasing liquid/solid (L/S) ratio and pH. Rebound of leachability was observed with high L/S ratio (> 60) and long-time leaching (> 30h). L/S ratio and pH were the most sensitive factors to the leachability of HMs with the corresponding contribution of 40.8% and 27.1%, respectively, followed by leaching time and temperature (~ 16%). The total contribution of global climate-associated factors, i.e., L/S ratio, leaching time, and temperature to the leachability of HMs was up to 70%, while leachate pH shared the other 30%. With the increase of persistent heavy rain in summer globally, As and Cd were found to having higher leaching risks than the other HMs in tailings, although an obvious decrease in their leachability was obtained due to the improvement of acid rain pollution in China. The study provides a valuable method for the identification of potential risk factors and their associations with the leaching behaviors of HMs in tailings under the background of obvious improvement on acid rain pollution in China and global climate change.