Immunotherapy efficacy is often constrained by an immunosuppressive tumor microenvironment deficient in functional antigen-presenting cells (APCs) and tumor-specific T cells. Here, we deploy lipid nanoparticles (LNPs) to deliver immune-remodeling mRNAs (IR-mRNAs) that reprogram tumor-resident immune cells in situ. IR-mRNAs activate APCs, expand cDC1 populations, enhance cytokine production, and drive robust CD8⁺ T cell priming. This approach induces durable anti-tumor immunity across multiple syngeneic tumor models following both intratumoral and systemic delivery. Mechanistically, IR-mRNA treatment promotes coordinated activation of myeloid and T cell compartments, restoring the cross-talk required for sustained anti-tumor responses. Co-delivery with antigen mRNA amplifies antigen-specific CD8⁺ T cell responses by approximately tenfold, supports the development of long-term immune memory, and prevents tumor growth in both prophylactic and therapeutic settings. In addition to their direct anti-tumor effects, IR-mRNAs function as potent vaccine adjuvants, enhancing both cellular and humoral immunity. By breaking myeloid immune suppression and promoting effective antigen presentation, this strategy enables coordinated adaptive immune responses within otherwise non-permissive tumors. Collectively, these findings establish IR-mRNA delivery as a versatile and programmable platform for immune reprogramming, with broad potential to improve immunotherapy across diverse cancer settings.