Nanomedicine provides a promising platform for the molecular treatment of disease. An ongoing challenge in nanomedicine is the targeted delivery of intravenously administered nanoparticles to particular tissues, which is of special interest in cancer. In this study, we show that the conjugation of iRGD peptides, which specifically target tumor neovasculature, to the surface of Physalis mottle virus (PhMV)-like nanoparticles leads to rapid cellular uptake in vitro and tumor homing in vivo. We then show that iRGD-targeted PhMV loaded with the chemotherapeutic doxorubicin shows increased potency in a murine flank xenograft model of cancer. Our results validate that PhMV-like nanoparticles can be targeted to tumors through iRGD-peptide conjugation and suggest that iRGD-PhMV provides a promising platform for the targeted delivery of molecular cargo to tumors.