Melanoma, a malignant skin tumor originating from melanocytes, is typically treated with surgery in its early stages. However, chemotherapy becomes the primary treatment as the disease progresses to intermediate and advanced stages. The parenteral administration of chemotherapy can cause anxiety, discomfort, and infection risks, especially in immunocompromised cancer patients. Additionally, the circulating drugs can lead to systemic toxicity and side effects. Microneedles (MNs) provide a safer, less invasive alternative to address these issues. Herein, we demonstrated the effectiveness of integrating antimicrobial MNs with combined photothermal and chemotherapy treatment modalities against melanoma, presenting a promising approach to improving cancer treatment outcomes while minimizing associated risks. By leveraging the unique properties of chitosan (CS) and the versatility of poly(vinyl alcohol) (PVA), we fabricated physically cross-linked MNs with inherent antibacterial and antiviral properties. The physical cross-linked network not only accommodated polypyrrole nanoparticles (PPy NPs) for photothermal capabilities but also facilitated drug [doxorubicin hydrochloride (DOX)] loading and release over an extended period. Interestingly, in vitro and in vivo studies revealed that the MNs possess intrinsic antimelanoma properties. Compared to monotherapies, the combination of photothermal therapy and chemotherapy exhibited enhanced effectiveness against melanoma. This research paves the way for safer, more effective cancer treatment strategies.