Tumor-associated macrophages (TAMs) play a critical role in the immunosuppressive solid tumor microenvironment, yet in situ engineering of TAMs for enhanced tumor immunotherapy remains a significant challenge in translational immune-oncology. Here, we report an innovative nanodrug-delivering-drug (STNSP@ELE) strategy that leverages two-dimensional (2D) stanene-based nanosheets (STNSP) and β-Elemene (ELE), a small-molecule anticancer drug, to overcome TAM-mediated immunosuppression and improve chemo-immunotherapy. Our results demonstrate that both STNSP and β-Elemene are capable of polarizing the tumor-supportive M2-like TAMs into tumor-suppressive M1-like phenotype, which acts with the ELE chemotherapeutic to booster anti-tumor responses. In vivo mouse studies demonstrate that STNSP@ELE treatment can reprogram the immunosuppressive TME by significantly increasing the intra-tumoral ratio of M1/M2-like TAMs, enhancing the population of CD4+ and CD8+ T lymphocytes and mature dendritic cells, and elevating the expression of immunostimulatory cytokines in B16F10 melanomas, thereby promoting a robust anti-tumor response. Our study not only demonstrates that the STNSP@ELE chemo-immunotherapeutic nanoplatform has immune-modulatory capabilities that can overcome TAM-mediated immunosuppression in solid tumors, but also highlights the promise of this nanodrug-delivering-drug strategy in developing other nano-immunotherapeutics and treating various types of immunosuppressive tumors.