Currently, immunochemotherapy based on tumor-associated macrophages (TAMs) is mainly used for elimination of M2 macrophages. However, these methods cannot make full use of the positive immune-modulatory effects of macrophages. This study explores a two-way cruise strategy for combining immunotherapy based on TAM phenotype reversal with classical chemotherapy, the nanosatellites (DOX@HFn-PGZL@Res) are proposed to accurately deliver the chemotherapeutic agents and immune activators to their respective target cells. When the delivery system is recruited to tumor microenvironment, the nanosatellites are separated into DOX@HFn and Res@GZL nanoparticles, which can enter cancer cells and M2-TAMs, respectively. The data show that DOX@HFn-PGZL@Res successfully re-educate M2 to M1 macrophages, resulting in an activated immune response and inhibition of tumor invasion and metastasis. In general, this work describes a two-way homing nanoplatform for the integration of immunotherapy and chemotherapy, which provides a new idea for the "attack-defense" integrated treatment of tumor.