<p>Melanoma is a very aggressive and lethal type of skin cancer involving pigment-producing melanocytes. Delivery of therapeutics to the target site of malignant cells in the skin with the application of the microneedle (MN) technique is considered the most effective and feasible of all the methods currently available. MNs are tiny structures with the potential to pierce the impervious stratum corneum layer of the skin and deliver the loaded drugs either inside the viable epidermis or the dermis in a non-invasive and painless manner. The widespread application of MNs to treat various diseases, including diabetes, wounds, and skin diseases, stems from their effective and safe delivery of drugs. However, conventional MNs are unable to deliver the therapeutics without adequate control. This issue can be circumvented by on-demand drug delivery using novel intelligent or smart stimuli-responsive MNs, which would release the loaded drug in a spatiotemporal control fashion upon exposure to external or internal stimuli. This review primarily focuses on different types of MNs, with the main emphasis on stimuli-responsive MNs, physical and physiological stimuli, and their applications in the treatment of melanoma. Additionally, this review provides a brief overview of transdermal drug delivery, melanoma, and its treatment options, as well as patents on stimulus-responsive MNs in the treatment of melanoma. It is anticipated that this review will provide some insight into the progress and development in this research area.</p> Graphical Abstract <p></p> <p>Smart MNs respond to the environment: physical or exogenous and physiological or endogenous stimuli and releasing therapeutic molecules at the melanoma site.</p>