The antitumor effects of conventional drug carriers are often attenuated and limited in application by biological barriers associated with tumor heterogeneity and resistance brought about by low tumor immunogenicity. With the rapid development of nanotechnology, naturally derived bioactive materials, and live cell carriers, a promising strategy emerges for targeting the tumor microenvironment (TME) for precision cancer therapy. The unique injury-targeting properties of platelets can significantly extend functional activity, which cannot be achieved with conventional nanocarriers. In this review, three strategies based on platelet-engineered materials are systematically described, namely nanoparticles for platelet membrane camouflage, engineered activated platelets, and targeted-platelets nanosystems. Platelet-based nanomaterials can effectively coordinate local and distant tumor-host crosstalk with controlled active tumor site recognition and killing effects due to the presence of specific membrane proteins on the surface and the self-secretion of a large number of particles. Further advances in platelets for effectively overcoming biological barriers and reducing immune resistance in cancer immunotherapy applications will be discussed in future clinical practice. This review provides an overview of recent research advances in platelet-based bioactive material-directed immunotherapy and chemotherapy to inform future antitumor combination therapies.