The escalating global challenge of bacterial skin infections is significantly compounded by the rapid emergence of antimicrobial resistance (AMR), which undermines the efficacy of conventional therapeutic protocols. This investigation was conducted to isolate and characterize prevalent bacterial pathogens from diverse skin manifestations and to evaluate their susceptibility profiles against commonly prescribed antibiotics. In this cross-sectional study, 145 clinical specimens were collected and subjected to rigorous microbiological and biochemical identification. Antimicrobial susceptibility testing was performed using the Kirby–Bauer disk diffusion method against five standard antibiotics. The results revealed a high isolation rate, with confirmed bacterial growth in 115 specimens (79.3%). Staphylococcus aureus was identified as the predominant pathogen, followed by Pseudomonas aeruginosa and Staphylococcus epidermidis. Notably, four specific isolates exhibited multi-drug resistance to the tested antibiotics. To address this, the study explored the bioactivity of fungal melanin as a natural antimicrobial alternative. Fungal melanin demonstrated potent antibacterial efficacy against these resistant strains, achieving a Minimum Inhibitory Concentration (MIC) of 16 µg/mL and a Minimum Bactericidal Concentration (MBC) of 32 µg/mL. These findings highlight the critical prevalence of Staphylococcal species in dermatological infections and the alarming trajectory of resistance development. The study concludes that fungal melanin possesses significant potential as a robust natural antimicrobial agent or adjunct therapy, offering a promising strategy to combat resistant bacterial skin infections in the face of dwindling antibiotic effectiveness.