Simple SummaryNon-melanoma skin cancers, including basal cell carcinoma and squamous cell carcinoma, are the most common types of cancer in the United States. In recent years, research into the tumor microenvironment of these cancers has shed light on the intricate network of cellular and acellular components surrounding tumor cells. This review aims to provide a deeper understanding of the complex interactions that occur within the tumor microenvironment and suggest potential therapies.AbstractIt is widely known that tumor cells of basal and squamous cell carcinoma interact with the cellular and acellular components of the tumor microenvironment to promote tumor growth and progression. While this environment differs for basal and squamous cell carcinoma, the cellular players within both create an immunosuppressed environment by downregulating effector CD4+ and CD8+ T cells and promoting the release of pro-oncogenic Th2 cytokines. Understanding the crosstalk that occurs within the tumor microenvironment has led to the development of immunotherapeutic agents, including vismodegib and cemiplimab to treat BCC and SCC, respectively. However, further investigation of the TME will provide the opportunity to discover novel treatment options.