Peritoneal metastases (PMs) occur due to the metastasis of gynecological and gastrointestinal cancers such as ovarian, colon, pancreatic, or gastric tumors. PM outgrowth is often fatal, and patients with PMs have a median survival of 6 months. Cowpea mosaic virus (CPMV) has been shown, when injected intratumorally, to act as an immunomodulator reversing the immunosuppressive tumor microenvironment, therefore turning cold tumors hot and priming systemic antitumor immunity. However, not all tumors are injectable, and PMs especially will require targeted treatments to direct CPMV toward the disseminated tumor nodules. Toward this goal, we designed and tested a CPMV nanoparticle targeted to S100A9, a key immune mediator for many cancer types indicated in cancer growth, invasiveness, and metastasis. Here, we chose to use an intraperitoneal (IP) colon cancer model, and analysis of IP gavage fluid demonstrates that S100A9 is upregulated following IP challenge. S100A9-targeted CPMV particles displaying peptide ligands specific for S100A9 homed to IP-disseminated tumors, and treatment led to improved survival and decreased tumor burden. Targeting CPMV to S100A9 improves preclinical outcomes and harbors the potential of utilizing CPMV for the treatment of IP-disseminated diseases.