Nickel smelting slag contains high-grade iron and nickel and represents a valuable secondary resource, yet it is often relegated to disposal. Hydrothermal leaching is a prevalent technique for recovering valuable metals from nickel smelting slag. Due to the limited research on the process mechanism, the leaching effectiveness of iron and other valuable metals remains low. Typically the leaching solution is used mainly to recover nickel, with iron being discarded as an impurity, resulting in significant losses of target metal in the iron-rich solution. This paper introduces novel techniques for the synergistic regulation of cascade high-value recovery of iron−nickel from ammonia oxide leaching and phosphoric acid from nickel smelting slag, achieving efficient leaching of iron−nickel and the production of high-purity iron phosphate and a nickel-enriched solution. The mechanism of gradual leaching and nickel-amine stabilization of the key phases of nickel smelting slag controlled by diffusion under the action of ammonium persulfate was elucidated. The separation of iron and nickel in iron-rich solution was achieved by using different phosphate K sp . Homogeneous 1 μm spherical FePO 4 and nickel enrichment solution were synthesized. Also, the key control strategies of the process were outlined. This study provides a feasible approach for the resource utilization of solid waste from nonferrous metal smelting, especially the metal extraction, separation, and high-value utilization of iron-rich polymetallic waste residue.