Antibiotic resistance is currently becoming a more serious threat to global health, especially in severe nosocomial infections treatment by multidrug-resistant bacteria. This research provides a new way of synergizing green-synthesis for zinc oxide quantum dots (ZnO-QDs with hexagonal crystals) that are 7nm in diameter and zero-valent Ag cubic crystals that are 67 nm in size embedded with nitazoxanide substrate (NZ). Instrumental characterization like SEM, TEM, EDAX, and FT-IR and comprehensive antimicrobial studies were conducted to study the incorporation behavior of composites based on Ag NPs/ZnO QDs/NAZ. This combination has not been hitherto addressed anywhere else in the published literature, as well as commercial viability. In this context, we have precisely tuned nanoparticle to nitazoxanide ratio for designing the formulation demonstrating potent activity against MDR infections. By employing nitazoxanide as a scaffold and careful decoration thereof antimicrobial potency has been unlocked overriding conventional therapies. In addition, Ag NPs/ZnO-QDs/nitazoxanide (G6) formula exhibited a therapeutic efficacy span of 96.15±1.68% to 99.57±0.20% against MDR human infections post 48h incubation; a breakthrough in therapeutic efficacy levels has been achieved by our method. Accordingly, ZnO QDs/Ag NPs/NZ composite offered potential multidrug resistant human pathogens as a new trend of revolutionizing antimicrobial treatment.