The extracellular matrix (ECM) plays a critical role in regulating cancer progression by modulating key biological processes known as the hallmarks of cancer. These hallmarks include sustained proliferation, evasion of growth suppression, resistance to death, replicative immortality, angiogenesis, invasion, dysregulation of cellular energetics, and avoidance of immune destruction. The ECM provides biochemical and biomechanical cues that influence these processes, shaping the tumor microenvironment and promoting malignancy. The ECM is dynamically remodeled in cancer, and its composition and mechanical properties can influence tumor behavior and therapeutic responses. For example, a stiffened ECM promotes cell proliferation, enhances angiogenesis, and supports metastasis by modulating signaling pathways such as ERK, PI3K, and Rac. The ECM also influences the ability of cancer cells to resist apoptosis by promoting survival signals and inhibiting tumor suppressor pathways. Additionally, the ECM can regulate metabolic reprogramming in cancer cells, favoring anaerobic glycolysis for rapid growth. The ECM's role in tumor progression is further highlighted by its influence on immune responses, where it can either support or inhibit immune surveillance. The ECM's biomechanical properties, such as stiffness, can also affect the tumor's interaction with the immune system and its ability to evade immune destruction. Understanding the ECM's role in cancer is essential for developing effective therapies, as targeting ECM components or signaling pathways could enhance conventional treatments. However, the complexity of the ECM and its interactions with tumor cells and the immune system presents challenges in translating these findings into clinical applications. Future research should focus on elucidating the ECM's role in different cancer types and its dynamic changes during tumor progression to develop more effective therapeutic strategies.The extracellular matrix (ECM) plays a critical role in regulating cancer progression by modulating key biological processes known as the hallmarks of cancer. These hallmarks include sustained proliferation, evasion of growth suppression, resistance to death, replicative immortality, angiogenesis, invasion, dysregulation of cellular energetics, and avoidance of immune destruction. The ECM provides biochemical and biomechanical cues that influence these processes, shaping the tumor microenvironment and promoting malignancy. The ECM is dynamically remodeled in cancer, and its composition and mechanical properties can influence tumor behavior and therapeutic responses. For example, a stiffened ECM promotes cell proliferation, enhances angiogenesis, and supports metastasis by modulating signaling pathways such as ERK, PI3K, and Rac. The ECM also influences the ability of cancer cells to resist apoptosis by promoting survival signals and inhibiting tumor suppressor pathways. Additionally, the ECM can regulate metabolic reprogramming in cancer cells, favoring anaerobic glycolysis for rapid growth. The ECM's role in tumor progression is further highlighted by its influence on immune responses, where it can either support or inhibit immune surveillance. The ECM's biomechanical properties, such as stiffness, can also affect the tumor's interaction with the immune system and its ability to evade immune destruction. Understanding the ECM's role in cancer is essential for developing effective therapies, as targeting ECM components or signaling pathways could enhance conventional treatments. However, the complexity of the ECM and its interactions with tumor cells and the immune system presents challenges in translating these findings into clinical applications. Future research should focus on elucidating the ECM's role in different cancer types and its dynamic changes during tumor progression to develop more effective therapeutic strategies.