During surgical procedures, skin and soft tissue wounds are often infected by resistant strains of gram-positive bacteria and gram-negative bacteria, resulting in serious obstacles to the healing of these wounds. Commercially available dressings for such wounds are still insufficient to combat resistant infections. Here, we designed vancomycin and epigallocatechin gallate (EGCG) loaded poly(vinyl)-pyrrolidone-gelatine nanofiber's membrane dressing for potential synergistic efficiency against infected post-surgical wounds. The nanofiber's membrane was physiochemically characterized by surface morphology, chemical and physical compatibilities', thermal stability, and drug release. Disk diffusion assays, Minimum inhibitor concentrations (MICs), and fractional inhibitory concentration indexes (FICI) were measured to analyze synergistic efficiency against Escherichia coli. Furthermore, Balb/c mice were used for in vivo healing studies, and to observe the healing mechanisms, histological assessments were performed. The designed system displayed excellent physical and chemical properties. The in vitro studies unveiled controlled-release patterns of vancomycin and EGCG and, at the same time, revealed 1.5-fold higher antimicrobial synergistic efficacy (FICI 0.485) than vancomycin against E. coli. The wound healing mechanisms reflected quick and mature healing processes with the promotion of collagen and angiogenesis at wound sites. The designed electrospun nanofiber technology might be personalized, rapid wound healing remedy for scientists and healthcare providers, and may enhance patients' outcomes and quality of life.