Penile squamous cell carcinoma is a rare condition that is associated with significant morbidity and mortality in its advanced stages. In today’s rapidly evolving field of oncology, physicians and scientists are learning to harness the power of genomics to drive innovative targeted, immunotherapeutic, and multimodal strategies across different cancer types; however, there remains a pressing need for a deeper understanding of the molecular pathways of penile carcinogenesis in order to help direct individualized therapy for patients with this disease.