Simple SummaryCutaneous side effects are among the most frequently reported adverse reactions of modern dermato-oncological therapies, such as immune checkpoint inhibitors and targeted therapies. This study aims to provide a detailed overview of the cutaneous toxicity profile of these treatments to facilitate physicians’ early recognition of these side effects. Furthermore, we aim to accentuate the need for a dermatological evaluation of the affected patients, as it can significantly affect the patient’s quality of life and the decision to continue treatment.AbstractThe advent of immunotherapy and targeted therapies in treating dermatological malignancies has dramatically changed the landscape of dermato-oncology in recent years. Their superior efficacy compared to previous therapeutic options, such as chemotherapy, has resulted in their use in treating devastating malignancies, such as melanoma or unresectable/metastatic basal cell and squamous cell carcinoma. Skin toxicity is a critical safety consideration, among other adverse reactions, that can occur under treatment with these agents. This article aims to summarize the cutaneous side effects of immune checkpoint inhibitors and targeted dermato-oncological therapies. Although the skin side effects of these agents are primarily mild, they can occasionally affect the decision for treatment continuation and the quality of life of the affected patients. Therefore, physicians must be acquainted with the specific cutaneous toxicity profile of such treatments to mitigate their impact on the patients and optimize the overall outcome of dermato-oncological therapy.