The extracellular matrix (ECM) plays a crucial role in the tumor microenvironment (TME), influencing tumor development, metastasis, and therapeutic efficacy. T lymphocytes, a key component of the immune system, interact with the ECM to regulate tumor cell behavior and immune responses. The ECM's composition, structure, and stiffness can be altered by tumor cells and stromal cells, affecting T cell function and infiltration. T cells express various ECM receptors, such as integrins, discoidin domain receptors (DDR), leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), CD44, and syndecan (SDC), which mediate these interactions. These interactions influence T cell activation, proliferation, and migration, impacting tumor progression and immune escape. Targeting ECM components, receptors, and related cytokines offers potential strategies for enhancing anti-tumor immune responses. Additionally, engineering T cells to modulate ECM and improving drug delivery systems targeting the ECM are promising approaches to enhance therapeutic efficacy. Bioprinting technology can also be used to study these interactions in a more physiological context. Overall, understanding and manipulating ECM-T cell interactions hold significant promise for developing novel cancer therapies.The extracellular matrix (ECM) plays a crucial role in the tumor microenvironment (TME), influencing tumor development, metastasis, and therapeutic efficacy. T lymphocytes, a key component of the immune system, interact with the ECM to regulate tumor cell behavior and immune responses. The ECM's composition, structure, and stiffness can be altered by tumor cells and stromal cells, affecting T cell function and infiltration. T cells express various ECM receptors, such as integrins, discoidin domain receptors (DDR), leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), CD44, and syndecan (SDC), which mediate these interactions. These interactions influence T cell activation, proliferation, and migration, impacting tumor progression and immune escape. Targeting ECM components, receptors, and related cytokines offers potential strategies for enhancing anti-tumor immune responses. Additionally, engineering T cells to modulate ECM and improving drug delivery systems targeting the ECM are promising approaches to enhance therapeutic efficacy. Bioprinting technology can also be used to study these interactions in a more physiological context. Overall, understanding and manipulating ECM-T cell interactions hold significant promise for developing novel cancer therapies.