The tumor microenvironment (TME) is characterized by a complex array of factors, including aerobic conditions, high glutathione (GSH) levels, acidic pH, and elevated hydrogen peroxide (HO) content, all of which promote cancer progression and contribute to poor prognosis. Fortunately, these challenges can be addressed using MnO-based nanomaterials. In this study, we have designed and synthesized a Curcumin/MnO@PLGA@4T1 cell membrane (CMP@4T1m) system aimed at remodelling the TME and enhancing sonodynamic immunotherapy for breast cancer. Through the homologous targeting ability of 4T1m, CMP@4T1m efficiently accumulates at the tumor site. Upon ultrasound irradiation, curcumin (Cur) acts as a sonosensitizer, generating cytotoxic reactive oxygen species (ROS) that induce immunogenic cell death (ICD), activate T-cell responses, and repolarize protumoral M2-like macrophages to antitumoral M1-like macrophages. In the TME, which is mildly acidic and enriched with GSH and HO, MnO not only oxidizes GSH to glutathione disulfide (GSSG) but also reacts with HO and H to produce oxygen, alleviating hypoxia and significantly enhancing the sonodynamic immunotherapy effect. Additionally, Mn generated during this process converts HO into cytotoxic hydroxyl radicals (˙OH). This study thus lays the foundation for advancing cancer nanomedicine, offering a novel approach that integrates TME remodelling with sonodynamic immunotherapy.