It is extremely important to develop a minimally invasive and efficient approach for treatment of superficial skin tumors (SSTs). In this work, a near-infrared (NIR)-triggered transdermal therapeutic system based on two-stage separable microneedles (MNs) has been proposed for synergistic chemo-photothermal therapy against SSTs. Lauric acid and polycaprolactone as phase-change materials have been used to prepare the arrowheads of the two-stage separable MNs in which an anticancer drug (doxorubicin, DOX) and photothermal agent (indocyanine green, ICG) were embedded. The arrowheads are capped on the dissolvable support bases that consisted of poly(vinyl alcohol)/polyvinyl pyrrolidone (PVA/PVP). After inserting into skin tissue, the PVA/PVP support bases can be dissolved quickly owing to the absorption of the interstitial fluid, leading the arrowheads to be left in the skin tissue. Under NIR irradiation, the arrowheads embedded in the skin can be ablated because of the photothermal conversion of the ICG, resulting in liberation and penetration of the DOX from the MNs into the tumor tissue. A mouse model of melanoma tumor has been established to evaluate the synergistic effect of two-stage separable MN phototherapy and chemotherapy in the treatment of skin cancer.