Cancer is the leading cause of death worldwide. Central to an effective immunotherapeutic treatment is the generation of CD8+ cytotoxic T lymphocyte responses to the malignant cells. Dendritic cells (DCs) are the key target in cancer immunotherapy. DCs recognize pathogens, initiate the immune response, and are capable of cross-presentation for the induction of CD8 T cell responses. DC-based cancer immunotherapies have been in trials in humans. Nanoparticles, as a vaccine carrier, have shown efficacy in antigen delivery by directly targeting DCs. This chapter examines how prophylactic and therapeutic tumor immunities can be achieved using nanoparticles targeting DCs in vivo. Moreover, this review elucidates the differential immunological properties of engineered nanoparticles. Surface morphology, size, shape, and surface functionalization can influence cellular uptake, toxicity, immunogenicity, and the T-helper 1 (Th1)/T-helper 2 (Th2) bias of the immune response. Understanding how nanoparticles with finely tuned properties interact and modulate the immune response will drive the logical development of nanoparticle vaccines to achieve the intended immunological response.