This review explores the complex interactions between T lymphocytes and the extracellular matrix (ECM) in the tumor microenvironment (TME), highlighting their roles in tumor development, immune evasion, and immunotherapy. The ECM, composed of proteins, glycans, and proteoglycans, plays a critical role in tumor progression by influencing T cell function, infiltration, and immune responses. T cells, in turn, regulate ECM synthesis, degradation, and remodeling through the secretion of cytokines and enzymes, which affects tumor cell proliferation, invasion, and immunotherapy efficacy. The interaction between T cells and the ECM is bidirectional, with the ECM modulating T cell activation, migration, and function, while T cells influence ECM composition and structure. The ECM's physical properties, such as stiffness and density, significantly impact T cell behavior, with increased stiffness promoting tumor growth and immune evasion. Tumor-associated fibroblasts (CAFs) and other stromal cells contribute to ECM remodeling, which can suppress immune responses by limiting T cell infiltration and promoting immunosuppressive environments. Key ECM components, such as collagen and hyaluronic acid, are involved in tumor progression and immune evasion, with their dysregulation contributing to tumor resistance to immunotherapy. Targeting the ECM presents a promising strategy for improving cancer immunotherapy. Approaches include inhibiting ECM components like collagen and hyaluronic acid, modulating ECM receptors, and using ECM-targeted drug delivery systems to enhance immune cell infiltration and drug efficacy. Additionally, bioprinting technologies are being explored to create 3D tumor models that simulate ECM-T cell interactions, aiding in the development of more effective therapies. Despite these advances, challenges remain in developing specific and safe ECM-targeted therapies that avoid adverse effects on normal tissues. Future research aims to address these challenges and improve the effectiveness of tumor immunotherapy by better understanding ECM-T cell interactions in the TME.This review explores the complex interactions between T lymphocytes and the extracellular matrix (ECM) in the tumor microenvironment (TME), highlighting their roles in tumor development, immune evasion, and immunotherapy. The ECM, composed of proteins, glycans, and proteoglycans, plays a critical role in tumor progression by influencing T cell function, infiltration, and immune responses. T cells, in turn, regulate ECM synthesis, degradation, and remodeling through the secretion of cytokines and enzymes, which affects tumor cell proliferation, invasion, and immunotherapy efficacy. The interaction between T cells and the ECM is bidirectional, with the ECM modulating T cell activation, migration, and function, while T cells influence ECM composition and structure. The ECM's physical properties, such as stiffness and density, significantly impact T cell behavior, with increased stiffness promoting tumor growth and immune evasion. Tumor-associated fibroblasts (CAFs) and other stromal cells contribute to ECM remodeling, which can suppress immune responses by limiting T cell infiltration and promoting immunosuppressive environments. Key ECM components, such as collagen and hyaluronic acid, are involved in tumor progression and immune evasion, with their dysregulation contributing to tumor resistance to immunotherapy. Targeting the ECM presents a promising strategy for improving cancer immunotherapy. Approaches include inhibiting ECM components like collagen and hyaluronic acid, modulating ECM receptors, and using ECM-targeted drug delivery systems to enhance immune cell infiltration and drug efficacy. Additionally, bioprinting technologies are being explored to create 3D tumor models that simulate ECM-T cell interactions, aiding in the development of more effective therapies. Despite these advances, challenges remain in developing specific and safe ECM-targeted therapies that avoid adverse effects on normal tissues. Future research aims to address these challenges and improve the effectiveness of tumor immunotherapy by better understanding ECM-T cell interactions in the TME.