Cancer is a complex disease affecting both humans and animals. Comparative immuno-oncology explores immune responses across species to develop effective cancer therapies. Oncolytic viruses (OVs) serve as both direct tumor-lysing agents and immune stimulants, making them an attractive therapeutic option. This review highlights the role of naturally occurring tumors in animal models for OV-based cancer immunotherapy. We examine immune responses in different species, the latest advancements in OV therapy, and the role of precision medicine in veterinary oncology. Understanding these comparative aspects enhances OV translation from preclinical to clinical applications in both veterinary and human oncology.