Comparative oncology leverages naturally occurring cancers in companion animals, particularly dogs, to bridge the gap between traditional laboratory models and real-world clinical trials in humans. This approach offers a potentially more accurate representation of tumor biology, treatment responses, and immunotherapy interactions compared to conventional mouse models. The establishment of the NIH Comparative Oncology Program and other collaborative networks has facilitated research that informs drug development, targeted therapies, and immuno-oncology treatments. While challenges remain, such as species-specific differences and regulatory complexities, comparative oncology has accelerated discoveries that benefit both human and veterinary medicine. Continued investment and collaboration between veterinary and human oncologists will be essential to maximizing its potential for advancing cancer treatment.