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Despite the importance and promise of cancer vaccines for broader prevention and treatment of cancer, limited clinical responses are observed, suggesting that key rational designs are required for inducing potent immune responses against cancer. Here we report a mesoporous silicon vector (MSV) as a multi-functional microparticle for formulating an efficient cancer vaccine composed of B16 melanoma derived-tyrosinase related protein 2 (TRP2) peptide and dual toll-like receptor (TLR) agonists. We demonstrated that MSV microparticles protected the peptide from rapid degradation for prolonged antigen presentation to immune cells. Moreover, MSV enabled co-delivery of two different TLR agonists [CpG oligonucleotide and monophosphoryl lipid A (MPLA)] along with TRP2 peptide into the same dendritic cell (DC), thus increasing the efficiency and capacity of DCs to induce potent TRP2-specifc CD8+ T cell responses against B16 melanoma. Furthermore, this MSV-based DC vaccine could significantly prolong the median survival of tumor-bearing mice by orchestrating effective host immune responses involving CD8+ T cells, CD4+ T cells and macrophages. Our study provides rational and potentially translational approach to develop durable and potent immunotherapy for patients with cancer by delivering various combinations of tumor antigens, neoantigens and innate immune agonists.Mesoporous silicon microparticles enabled co-delivery of tumor antigen and dual toll-like receptor ligands provide rational and potentially translational approach to develop durable and potent immunotherapy against cancer.