Overuse of antibiotics in the fish and shellfish production systems throughout time may be one of the primary causes of growing antibiotic resistance in bacteria. In this study, 90 samples of Nile Tilapia, Mugil, and shrimps were tested for the presence of Aeromonas and Pseudomonas species and monitored their antibiotic resistance pattern. The isolated bacterial strains were identified based on morphological and biochemical characteristics. Further, the isolates were tested against 14 antimicrobial agents using the disc diffusion method, and the multidrug resistance pattern was studied. The results showed that across the three sample types, Pseudomonas fluorescens (26.7%) and Aeromonas hydrophila (21.1%) were the most common, followed by A. caviae (14.4%), P. putrefaciens (13.3%), A. sobria (12.2%), P. fragi (11.1%), P. alcaligenes (10%), A. veronii (5.6%), P. proteolytica (4.4%), P. aeruginosa (3.3%), P. cepacian (2.2%), and A. fluvialis (1.1%). The two most common strains were submitted for susceptibility analysis that revealed multidrug-resistant. For Aeromonas hydrophila highest rates of resistance were to Streptomycin (100%) and Penicillin G (92.3%), then Erythromycin (84.6%) and Cefotaxime (84.6%). For Pseudomonas fluorescens highest rates of resistance were to Nalidixic acid (100%) and Streptomycin (100%), then Erythromycin (91.7%), Penicillin G (79.2%) and Cephalothin (75%). Pseudomonas fluorescens and Aeromonas hydrophila had average multiple antibiotic resistance indexes of 0.521 and 0.494, respectively. In conclusion, fish, and shellfish sold in the Egyptian market act as a reservoir for the multi-resistant Aeromonas and Pseudomonas genera. These significant findings call for effective risk assessment models and management plans that protect human, and animal.