Multi drug resistant (MDR) Staphylococcus spp. particularly the emerging Methicillin-resistant S. aureus (MRSA) strains are of serious zoonotic public health concern. The scope of this study was to analyze the incidence of Staphylococcus spp. with a focus on S. aureus and MRSA strains and evaluate their staphylococcal enterotoxins (SE) and resistance genes. A total of 330 samples of raw milk from animals (cows, buffaloes, sheep and goat) and Karish cheese (as a major risk for in dairy industry) were screened and examined. The prevalence ratio of S. aureus in raw milk (from examined farm animals or milk smallholders) and in cheese was 38.5% (127/330) however, non-S. aureus (NSA) was identified in 16.7% (55/330). Multi Drug Resistant (MDR) pattern of S. aureus isolates was exhibited with identification of MRSA strains in (44.9%). Penicillin showed the highest resistance level (55.1%) however, gentamycin was the most sensitive one. S. aureus strains were confirmed with the presence of nuc gene in 100% with PCR tool however, PCR for SE genes declared that seb was prevalent in 85.7% followed by sed and sea genes in (64.3% and 28.5%), respectively. Furthermore, β-lactam resistance (blaZ and mecA) genes were found in 100% and 50%, respectively. This data suggested that monitoring and surveillance plans with strict control measures in dairy farms should be applied to lessen the spread of MDR Staph spp. especially MRSA strains. Also, awareness of milk smallholders and farm workers must be raised to ensure the quality of raw milk for safe public health concern.