Multifunctional nanoplatforms show the synergistic effect of multiple treatment modalities and have become a research hotspot as they are superior to the antitumor properties of single treatment modes. In this work, we synthesized an similar to 115 nm liposome nanoparticle ergosterol peroxide/TMP195@liposome (EP/TMP195@lip). It releases the natural product, EP, and the repolarization agent of tumor-associated macrophages, TMP195, through escape of endosomes in breast cancer cells. EP/TMP195@lip could effectively inhibit the proliferation and migration of breast cancer cells and induce mitochondrial membrane potential damage and cell apoptosis by regulating the P53 signaling pathway. Besides, it reshapes the tumor microenvironment, transforming M2-like tumor-associated macrophages (TAMs) into M1-like TAMs to assist the immune cells in recognizing and eliminating tumor tissue. Furthermore, EP/TMP195@lip promotes the maturation and differentiation of dendritic cells and activates T cells, which enhances the effect of tumor immunotherapy. Taken together, EP/TMP195@lip is expected to provide high-quality strategies for safe and effective breast cancer immunotherapy.