Nonmelanoma skin cancer is the most prevalent cancer worldwide, and a number of cases are steadily increasing. The incidence of skin squamous cell carcinoma, which is the second most frequent tumor in this group of tumors, is markedly increasing in immunosuppressed transplant recipients and under certain cancer treatment modalities. Unfortunately, the aggressiveness of these tumors is also increasing, and once metastasized, the therapies to successfully eradicate these tumors are lacking, thus making research advancements vital. We firstly discuss what is currently known about cutaneous squamous cell carcinomas (cSCCs), an important consideration when designing relevant model systems for further investigation. We continue by reviewing recent studies, which have utilized different models and highlight the importance/requirement for human 3D models to combat this devastating tumor type.