Staphylococcus aureus is among the most common zoonotic pathogens originating from animals consumed as food, especially raw chicken meat (RCM). As far as we know, this might be the first report that explores the efficacy of metal oxide nanoparticles (MONPs), such as zinc peroxide nanoparticles (ZnO2-NPs), zinc oxide nanoparticles (ZnO-NPs), and titanium dioxide nanoparticles (TiO2-NPs) against multidrug resistant (MDR) and/ or pandrug resistant (PDR) S. aureus strains with a strong biofilm-producing ability isolated from RCM and giblets. The overall prevalence of coagulase-positive staphylococci was 21%, with a contamination level range between 102 and 104 CFU/g. The incidence of virulence genes See (21/36), pvl (16/36), clfA (15/36), sec (12/36), tst (12/36), and sea (11/36) among S. aureus strains were relatively higher those of seb, sed, fnbA, and fnbB. For antimicrobial resistance gene distribution, most strains harbored the blaZ gene (25/36), aacA-aphD gene (24/36), mecA gene (22/36), vanA gene (20/36), and apmA gene (20/36) confirmed the prevalence of MDR among S. aureus of RCM products. However, cfr (11/36), spc (9/36), and aadE (7/36) showed a relatively lower existence. The data of antibiogram resistance profiles was noticeably heterogeneous (25 patterns) with 32 MDR and four PDR S. aureus strains. All tested strains had a very high MAR index value (>0.2) except the P11 pattern (GEN, MXF, PMB), which showed a MAR index of 0.19. Among the strong biofilm-producing ability (BPA), 14 (70%) strains were isolated from wet markets, while only six strong BPA strains were isolated from supermarkets. The mean values of BPA ranged from 2.613 ± 0.04 to 11.013 ± 0.05. Clearly, ZnO2-NPs show significant inhibitory activity against S. aureus strains compared with those produced by the action of ZnO-NPs and TiO2- NPs. The results of anti-inflammatory activity suggest ZnO2-NPs as a lead compound for designing an alternative antimicrobial agent against drug-resistant and strong biofilm-producing S. aureus isolates from retail RCM and giblets.