Dendritic cell (DC) vaccines hold great potential in cancer immunotherapy, but the suboptimal design of DC vaccines and the immunosuppressive tumor microenvironment largely impair their anti-tumor efficacy. Here, quantum dot (QD) pulsed-DC vaccines integrating with tumor-associated macrophage polarization are developed for amplified anti-tumor immunity. Semiconductor QDs are engineered with diverse functions to act as fluorescence nanoprobes, immunomodulatory adjuvants, and nanocarriers to load tumor antigens and Toll-like receptor 9 agonists. The QD-pulsed DC vaccines enable spatiotemporal tracking of lymphatic drainage and efficacy evaluation of DC immunotherapy, and trigger potent immunoactivation. Specifically, designer DC vaccine plus macrophage polarization elicits potent immune response to stimulate innate and adaptive antitumor immunity and ameliorate the immunosuppressive tumor microenvironment. As a new combination therapy, this strategy greatly boosts antigen-specific T-cell immunity and thus strongly inhibits local tumor growth and tumor metastasis in vivo. This study may provide an applicable treatment for cancer immunotherapy.