CD8+ T cell-based cancer immunotherapy has shown promising results in treating intractable diseases, but tumors can evade immune surveillance by suppressing CD8+ T cell function. Understanding CD8+ T cell biology, tumor immune escape mechanisms, and developing effective immunotherapies are critical for clinical research. CD8+ T cells are key effectors in acquired immunity, and their activation requires three signals: TCR-MHC interaction, costimulatory signals, and cytokine signals. Activated CD8+ T cells can kill tumor cells through granzymes, perforins, and cytokines, or via EVs, Fas-L, or other pathways. However, tumor cells can downregulate MHC I, express immunosuppressive factors like IL-10, IDO1, and TGF-β, or release EVs to inhibit CD8+ T cell function. Tregs, DCs, and TAMs also contribute to immunosuppression by secreting inhibitory molecules and altering TME. Immune checkpoint inhibitors (ICIs), such as anti-PD-1/PD-L1, have revolutionized cancer treatment by reactivating CD8+ T cells. However, response rates remain low, and biomarkers like CD14+CD16b- HLA-DRhi and SMARCA4 mutations can predict ICI efficacy. Combination therapies, including ICIs with other agents, have shown improved outcomes. Neoantigen vaccines, which target tumor-specific antigens, have shown promise, especially when combined with ICIs or adjuvants. CAR-T and TCR-T cell therapies, which engineer T cells to recognize tumor antigens, have demonstrated efficacy in hematological malignancies but face challenges in solid tumors due to poor T cell infiltration and tumor immune escape. Adoptive cell therapy (ACT) involves isolating and expanding T cells ex vivo before reinfusion. TIL-ACT, which uses tumor-infiltrating lymphocytes, has shown success in melanoma and other cancers. Oncolytic virotherapy, such as T-VEC, uses modified viruses to lyse tumor cells and enhance immune responses. Nanomedicine, combined with immunotherapy, enhances drug delivery and targets TME, improving CD8+ T cell infiltration and antitumor immunity. These approaches highlight the importance of understanding CD8+ T cell biology and tumor immune evasion to develop effective cancer immunotherapies.CD8+ T cell-based cancer immunotherapy has shown promising results in treating intractable diseases, but tumors can evade immune surveillance by suppressing CD8+ T cell function. Understanding CD8+ T cell biology, tumor immune escape mechanisms, and developing effective immunotherapies are critical for clinical research. CD8+ T cells are key effectors in acquired immunity, and their activation requires three signals: TCR-MHC interaction, costimulatory signals, and cytokine signals. Activated CD8+ T cells can kill tumor cells through granzymes, perforins, and cytokines, or via EVs, Fas-L, or other pathways. However, tumor cells can downregulate MHC I, express immunosuppressive factors like IL-10, IDO1, and TGF-β, or release EVs to inhibit CD8+ T cell function. Tregs, DCs, and TAMs also contribute to immunosuppression by secreting inhibitory molecules and altering TME. Immune checkpoint inhibitors (ICIs), such as anti-PD-1/PD-L1, have revolutionized cancer treatment by reactivating CD8+ T cells. However, response rates remain low, and biomarkers like CD14+CD16b- HLA-DRhi and SMARCA4 mutations can predict ICI efficacy. Combination therapies, including ICIs with other agents, have shown improved outcomes. Neoantigen vaccines, which target tumor-specific antigens, have shown promise, especially when combined with ICIs or adjuvants. CAR-T and TCR-T cell therapies, which engineer T cells to recognize tumor antigens, have demonstrated efficacy in hematological malignancies but face challenges in solid tumors due to poor T cell infiltration and tumor immune escape. Adoptive cell therapy (ACT) involves isolating and expanding T cells ex vivo before reinfusion. TIL-ACT, which uses tumor-infiltrating lymphocytes, has shown success in melanoma and other cancers. Oncolytic virotherapy, such as T-VEC, uses modified viruses to lyse tumor cells and enhance immune responses. Nanomedicine, combined with immunotherapy, enhances drug delivery and targets TME, improving CD8+ T cell infiltration and antitumor immunity. These approaches highlight the importance of understanding CD8+ T cell biology and tumor immune evasion to develop effective cancer immunotherapies.