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In recent years, there has been a surge of interest in tumor microenvironment-associated cancer vaccine therapies. These innovative treatments aim to activate and enhance the body's natural immune response against cancer cells by utilizing specific antigens present in the tumor microenvironment. The goal is to achieve a complete clinical response, where all measurable cancer cells are either eliminated or greatly reduced in size. With their potential to revolutionize cancer treatment, these therapies represent a promising avenue for researchers and clinicians alike. Despite over 100 years of research, the success of therapeutic cancer vaccines has been variable, particularly in advanced cancer patients, with various limitations, including the heterogeneity of the tumor microenvironment, the presence of immunosuppressive cells, and the potential for tumor escape mechanisms. Additionally, the effectiveness of these therapies may be limited by the variability of the patient's immune system response and the difficulty in identifying appropriate antigens for each patient. Despite these challenges, tumor microenvironment-targeted vaccine cancer therapies have shown promising results in preclinical and clinical studies and have the potential to become a valuable addition to current cancer treatment and "curative" options. While chemotherapeutic and monoclonal antibody treatments remain popular, ongoing research is needed to optimize the design and delivery of these therapies and to identify biomarkers that can predict response and guide patient selection. This comprehensive review explores the mechanisms of cancer vaccines, various delivery methods, and the role of adjuvants in improving treatment outcomes. It also discusses the historical background of cancer vaccine research and examines the current state of major cancer vaccination immunotherapies. Furthermore, the limitations and effectiveness of each vaccine type are analyzed, providing insights into the future of cancer vaccine development.