To address long-standing issues with tumor penetration and targeting among cancer therapeutics, we developed an anticancer platelet-based biomimetic formulation (N+R@PLTs), integrating photothermal nanoparticles (N) and immunostimulator (R) into platelets (PLTs). Exploiting the aggregative properties of platelets and high photothermal capacity, N+R@PLTs functioned as an arsenal by targeting defective tumor vascular endothelial cells, accumulating in a positive feedback aggregation cascade at sites of acute vascular damage induced by N-generated local hyperthermia, and subsequently secreting nanosized proplatelets (nPLTs) to transport active components to deep tumor tissue. The immunostimulator augmented the immunogenicity of antigens released from ablated tumors, inducing a stronger immunological response to attack residual, metastatic, and recurrent tumors. Following activation by low-power near-infrared light irradiation, the photothermal and immunological components synergistically provide exceptionally high therapeutic efficacy across nine murine models that mimicked a range of clinical requirements, and, most notably, a sophisticated model based on humanized mouse and patient-derived tumor xenograft.