<p>Immunologically cold tumors present a significant challenge in cancer treatment due to their limited baseline immune infiltration and resistance to immunotherapy. Cancer vaccines offer a promising strategy to overcome this barrier by introducing high-quality, tumor-relevant antigens that can stimulate an effective anti-tumor immune response. Therapeutic cancer vaccines are being explored in the neoadjuvant, adjuvant, and minimal residual disease contexts to enhance immune activation and promote immune cell infiltration and function, with the goal to eradicate malignant cells and improve patient survival. Critical hurdles remain in optimizing antigen selection, determining the most effective vaccine formulations, and defining the ideal clinical setting for vaccine use. Moreover, rational combinations of cancer vaccines with other immune modulators (e.g., adjuvants, immune checkpoint inhibitors, and cytokines) may hold the key to enhancing vaccine efficacy and expanding therapeutic options for difficult-to-treat malignancies. This review examines current advancements in cancer vaccines and their utilization for immunologically cold tumors in the perioperative setting, highlighting ongoing challenges and future directions in this evolving field. </p>