To explore the relationship between cadmium (Cd) and zinc (Zn) uptake in Sedum plumbizincicola and the supply of soil cation nutrient elements, and guide the enhancement of phytoextraction performance of hyperaccumulators from the perspective of nutrient regulation, a pot experiment was conducted in 49 soils with different types, cultivation methods, and pollution levels collected from the southern China. Plant growth and metal uptake of Sedum plumbizincicola were studied, and correlation analysis and Generalized Boosted Models were used to find the key cation nutrient factors controlling metal uptake in plants. The results showed that: 1)Soil total manganese (Mn) and iron (Fe) were the main nutrient factors affecting shoot biomass of Sedum plumbizincicola, with contribution rates of 34.61% and 16.31%, respectively. 2) The available calcium (Ca) and total magnesium (Mg) were significantly positively correlated with shoot Cd concentration and uptake. Their contribution rates to shoot Cd concentration were 16.90% and 10.39%, respectively. The contribution rate of available Mg to shoot Cd concentration was 14.21%. Available Mn showed the greatest impact on Zn accumulation in Sedum plumbizincicola, with its contribution rates to shoot Zn concentration and uptake of 17.76% and 20.86%, respectively. In summary, the supplies of soil cation nutrients affect the growth and metal uptake of Sedum plumbizincicola to a certain extent, among which soil Mg and Mn supplies are two major important factors. Via regulating nutrient supply, it can enhance Cd and Zn uptake by Sedum plumbizincicola, thereby improving metal removal efficiency in the contaminated soils.