Introduction: Milk is an important food in Egypt and most of it is sold as raw milk in informal markets. Methodology: This study was conducted to investigate the public health risks of Escherichia coli and Staphylococcus aureus in milk sold in informal markets in Egypt. A total of 121 milk samples were analyzed for occurrence, virulence genes and antibiotic resistance of E. coli and S. aureus. Results: A total of 35/121 (28.9%) of milk samples were contaminated with 16/121 (13.2%) E. coli, 22/121 (18.2%) S. aureus, and 3/121 (2.5%) both isolates. Shiga-toxin producing E. coli (STEC), Enterotoxigenic E. coli (ETEC) and Enterotoxigenic S. aureus were detected in 5/121 (4.1%), 2/121 (1.7%) and 8/121 (6.6%) of the examined milk samples, respectively. Multiple drug resistances (MDRs) were showed by 14/16 (87.5%) and 21/22 (95.5%) of E. coli and S. aureus isolates, respectively. E. coli isolates showed high resistance for cephalothin (87.5%), ampicillin (68.8%) and tetracycline (68.8%), but were sensitive for gentamicin and chloramphenicol. Resistance phenotypes of E. coli were diverse; however, STEC isolates were significantly associated with co-resistance to cephalothin, ampicillin and tetracycline (P< 0.05). Two (9.1%) of S. aureus isolates were methicillin-resistant (MRSA) but sensitive to gentamicin (GS-MRSA). Five (22.7%) of S. aureus isolates were gentamicin-resistant methicillin-sensitive S. aureus (GR-MSSA). S. aureus isolates also showed high resistance for ampicillin (100%), tetracycline (90.1%) and sulfamethoxazole-trimethoprim (90.1%). Conclusion: These findings highlighted the potential public health hazards of E. coli and S. aureus pathogens in raw milk sold in informal markets in Egypt.