Cancer immunotherapy has revolutionized oncology by using the immune system to combat cancer, with next-generation vaccines emerging as a transformative approach. The use of neo-antigens derived from tumor-specific mutations has significantly improved vaccine precision, enabling targeted immune activation against heterogeneous tumors. Furthermore, artificial intelligence (AI) is revolutionizing vaccine design by predicting the optimal antigen selection, optimizing immune epitopes, and personalizing therapies for each patient. We review recent advancements in cancer vaccine strategies, particularly neo-antigen-based and AI-driven personalized approaches to enhancing tumor-specific immune responses. The evolution of vaccine platforms, including dendritic cell vaccines, mRNA vaccines, and viral vector-based approaches, is highlighted with a focus on their mechanisms in generating strong antitumor immunity. These platforms not only differ in delivery efficiency and antigen expression but also offer unique immunological advantages. Combination strategies such as vaccines with immune checkpoint inhibitors, adoptive cell therapies (CAR-T, TCR-T), and tumor-infiltrating lymphocyte (TIL) therapy demonstrate synergistic effects in overcoming immune evasion and improving clinical outcomes. Despite these advancements, challenges such as tumor immunosuppression, antigen escape, and manufacturing scalability remain. Future directions highlight multi-omics integration, nanotechnology-based delivery systems, and biomarker-driven personalization to refine vaccine efficacy. The convergence of immunology, bioinformatics, and clinical oncology is essential to bring these innovations into routine clinical practice, enabling next-generation immunotherapies that maximize tumor eradication and long-term survival.