A novel low-temperature alkaline smelting process is proposed to convert and separate amphoteric metals in crushed metal enrichment originated from waste printed circuit boards. The central composite design was used to optimize the operating parameters, in which mass ratio of NaOH-to-CME, smelting temperature and smelting time were chosen as the variables, and the conversions of amphoteric metals tin, lead, aluminum and zinc were response parameters. Second-order polynomial models of high significance and 3D response surface plots were constructed to show the relationship between the responses and the variables. Optimum area of 80%-85% Pb conversion and over 95% Sn conversion was obtained by the overlaid contours at mass ratio of NaOH-to-CME of 4.5-5.0, smelting temperature of 653-723 K, smelting time of 90-120 min. The models were validated experimentally in the optimum area, and the results demonstrate that these models are reliable and accurate in predicting the smelting process.