Gamma/delta T cells (γδ T cells) are a promising cellular vehicle for anti-tumor immunotherapy due to their unique properties, including the ability to recognize a wide range of tumor ligands and their allogeneic potential. Unlike αβ T cells, which are HLA-restricted and limited to autologous use, γδ T cells can be used in allogeneic settings, reducing the risk of graft-versus-host disease (GvHD). These cells are found in low abundance in peripheral blood and umbilical cord blood but play critical roles in immune defense against infections and cancer. γδ T cells can recognize stressed cells, such as tumor cells, through various ligands, including butyrophilins (BTNs) and MHC class I-related chain A/B (MICA/MICB), and can directly kill these cells without prior antigen exposure. They also secrete effector molecules like IFN-γ and TNF-α, which enhance antitumor responses. γδ T cells have shown associations with both positive and negative prognostic outcomes in various cancers. For example, higher infiltration of γδ T cells in tumors is generally correlated with better survival in cancers like triple-negative breast cancer (TNBC), while certain subsets, such as regulatory γδ T cells (γδ Tregs), can promote tumor growth by suppressing immune responses. The role of γδ T cells in tumor immunity is complex, with different subsets exhibiting divergent functions. Understanding these subsets and their interactions with the tumor microenvironment (TME) is crucial for harnessing their therapeutic potential. Despite their advantages, challenges remain in the clinical application of γδ T cells. These include the need for better understanding of γδ T cell subsets, their ligands, and their functional roles in different tumor contexts. Additionally, the infiltration of γδ T cells into solid tumors is limited, and their anti-tumor activity can be suppressed by the immunosuppressive TME. Strategies to enhance γδ T cell function include optimizing ex vivo expansion conditions, using specific antigens or pharmacological agents to activate γδ T cells, and modifying them with chimeric antigen receptors (CARs) to target specific tumor antigens. These approaches aim to improve the anti-tumor efficacy and safety of γδ T cell therapies. Clinical trials have shown that γδ T cells can be safely administered, with minimal adverse events, but their therapeutic efficacy varies. Some trials have reported high complete response rates, particularly in hematological malignancies. However, more research is needed to optimize γδ T cell therapies, including improving their infiltration into solid tumors, enhancing their cytotoxicity, and ensuring their long-term survival in the TME. The future of γδ T cell immunotherapy lies in refining these strategies to maximize their potential in cancer treatment.Gamma/delta T cells (γδ T cells) are a promising cellular vehicle for anti-tumor immunotherapy due to their unique properties, including the ability to recognize a wide range of tumor ligands and their allogeneic potential. Unlike αβ T cells, which are HLA-restricted and limited to autologous use, γδ T cells can be used in allogeneic settings, reducing the risk of graft-versus-host disease (GvHD). These cells are found in low abundance in peripheral blood and umbilical cord blood but play critical roles in immune defense against infections and cancer. γδ T cells can recognize stressed cells, such as tumor cells, through various ligands, including butyrophilins (BTNs) and MHC class I-related chain A/B (MICA/MICB), and can directly kill these cells without prior antigen exposure. They also secrete effector molecules like IFN-γ and TNF-α, which enhance antitumor responses. γδ T cells have shown associations with both positive and negative prognostic outcomes in various cancers. For example, higher infiltration of γδ T cells in tumors is generally correlated with better survival in cancers like triple-negative breast cancer (TNBC), while certain subsets, such as regulatory γδ T cells (γδ Tregs), can promote tumor growth by suppressing immune responses. The role of γδ T cells in tumor immunity is complex, with different subsets exhibiting divergent functions. Understanding these subsets and their interactions with the tumor microenvironment (TME) is crucial for harnessing their therapeutic potential. Despite their advantages, challenges remain in the clinical application of γδ T cells. These include the need for better understanding of γδ T cell subsets, their ligands, and their functional roles in different tumor contexts. Additionally, the infiltration of γδ T cells into solid tumors is limited, and their anti-tumor activity can be suppressed by the immunosuppressive TME. Strategies to enhance γδ T cell function include optimizing ex vivo expansion conditions, using specific antigens or pharmacological agents to activate γδ T cells, and modifying them with chimeric antigen receptors (CARs) to target specific tumor antigens. These approaches aim to improve the anti-tumor efficacy and safety of γδ T cell therapies. Clinical trials have shown that γδ T cells can be safely administered, with minimal adverse events, but their therapeutic efficacy varies. Some trials have reported high complete response rates, particularly in hematological malignancies. However, more research is needed to optimize γδ T cell therapies, including improving their infiltration into solid tumors, enhancing their cytotoxicity, and ensuring their long-term survival in the TME. The future of γδ T cell immunotherapy lies in refining these strategies to maximize their potential in cancer treatment.