Photocarcinogenesis is primarily driven by ultraviolet (UV) radiation, is a multi-step process that results in melanoma, squamous cell carcinoma, and basal cell carcinoma. It causes DNA damage, mutational inactivation of tumor suppressors, and activation of oncogenes. Immunocompromised groups, such as organ transplant recipients and HIV-positive people, are especially vulnerable, with faster tumor growth, higher recurrence, and lower survival rates. When surgery is not viable, radiotherapy offers an alternative. The most prudent step toward these individuals remains the surgical excision with margin control; however, recurrence and higher wound complications limit the effectiveness of this procedure. The tumor burden can be reduced by preventive measures, such as modifying immunosuppressive regimens and using chemoprevention drugs like acitretin, capecitabine, and nicotinamide; however, long-term use is frequently limited due to toxicity. Targeted therapies and immune checkpoint inhibitors show emerging promise but raise concerns of graft rejection, drug interactions, and reduced efficacy under immunosuppression. Future efforts must prioritize prevention, therapeutic optimization, and dedicated trials in these vulnerable populations.