Damage-associated molecular patterns (DAMPs) are endogenous molecules released by cells in response to injury or stress, recognized by host pattern recognition receptors that assess the immunological significance of cellular damage. The interaction between DAMPs and innate immune receptors triggers sterile inflammation, which serves a dual purpose: promoting tissue repair and contributing to pathological conditions, including age-related diseases. Chronic inflammation mediated by DAMPs accelerates immunosenescence and influences both tumor progression and anti-tumor immunity, underscoring the critical role of DAMPs in the nexus between aging and cancer. This review explores the characteristics of immunosenescence and its impact on age-related cancers, investigates the various types of DAMPs, their release mechanisms during cell death, and the immune activation pathways they initiate. Additionally, we examine the therapeutic potential of targeting DAMPs in age-related diseases. A detailed understanding of DAMP-induced signal transduction could provide critical insights into immune regulation and support the development of innovative therapeutic strategies.