Comprehensive SummaryThe saline and buffered environment in actual wastewater imposes higher demands on Fenton and Fenton‐like catalytic systems. This study developed a MoS2 co‐catalytic Fe2O3 Fenton‐like system with controllable Lewis acid‐base sites, achieving efficient treatment of various model pollutants and actual industrial wastewater under neutral buffered environment. The acidic microenvironment structured by the edge S sites (Lewis basic sites) in the MoS2/Fe2O3 catalyst is susceptible to the influence of Lewis acidic sites constructed by Mo and Fe element, affecting catalytic performance. Optimizing the ratio of precursor amounts ensures the stable presence of the acidic microenvironment on the surface of catalyst, enabling the beneficial co‐catalytic effect of Mo sites to be realized. Furthermore, it transcends the rigid constraints imposed by the Fenton reaction on reaction environments, thereby expanding the applicability of commonplace oxides such as Fe2O3 in actual industrial water remediation.