Melanoma cancer wound healing is critical and complex and poses a significant challenge to researchers. Drug resistance, adverse side effects, and inefficient localization of chemotherapeutic drugs limit common treatment strategies in melanoma cancer. Using drug delivery nanostructures with low side effects and high efficiency, besides having antibacterial and antiseptic properties, can effectively repair the damage caused by the disease. To this end, this study aimed to develop a drug delivery nanosystem based on doxorubicin (DOX)-loaded amine-functionalized mesoporous silica nanoparticles (MSNs), linked with green synthesized silver nanoparticles (AgNPs). Characterization methods including microscopic methods and X-ray diffraction (XRD) confirmed the synthesis and functionalization of the well-dispersed nanoparticles with nanosized and uniform structures. The poly(ε-caprolactone) (PCL) nanofibers as a strong scaffold were produced by the blow spinning method and DOX-loaded nanoparticles were blow spun on PCL nanofibers along with gelatin solution. The resulting nanosystem including nanofibers and nanoparticles (NFs/NPS) showed a fine loading percent with a proper release profile of DOX and AgNPs and low hemolysis activity. Moreover, besides preventing infection by AgNPs, the DOX-loaded NFs/NPs could effectively destroy melanoma cancer cells. The attachment of normal cells to the nanoparticles-loaded nanofibers scaffold revealed the possibility of healing wounds caused by melanoma cancer.