Through deteriorating the quality of shrimp, Vibrio parahaemolyticus and heavy metals have become threatened to food safety. The study was conducted to explore shrimp and their environments for antibiotic resistance genes of V. parahaemolyticus and perform spectrophotometry of shrimp muscles for heavy metals and their human health risk assessment. In total, 130 samples (shrimp, water, and sediment) were aseptically collected from 27 ponds in four areas of Khulna and Satkhira districts where the number of water and sediments were corresponded to the number of ponds and the number of shrimps differed from pond to pond. V. parahaemolyticus were detected by cultural, staining, biochemical, and molecular techniques targeting groEL, tetA, tetB, tetC, and blaTEM genes. Disc diffusion assay and bivariate analysis were performed for investigating antibiotic resistance profiles of V. parahaemolyticus. Cadmium, chromium, lead, zinc, and iron were measured by AAS (atomic absorption spectrometry) in shrimp. Among 39 isolates (23 from shrimp, 7 from water, 9 from sediment), real-time PCR (polymerase chain reaction) detected 20 of 27 as positive for groEL, 12 of 20 for tetA, 13 for tetB, 12 for tetC, and 1 for blaTEM. V. parahaemolyticus were highly resistant to tetracycline and ampicillin. Bivariate analysis revealed a significant correlation between the antibiotics. 51.28% isolates were MDR (multidrug resistant), and the MAR (multiple antibiotic resistance) indices ranged from 0.08-0.6. The highest average concentration for Cd was in Debhata, Pb in Dumuria, Cr in Kaliganj, Zn and Fe in Satkhira Sadar. THQ (target hazard quotients) of >1 for Fe in all sampling sites showed higher level of HI (hazard index). No determined TR (target cancer risk) value exceeded the recommended value (<10-4). The study emphasizes the significance of adopting extensive surveillance and monitoring of a large number of shrimp farms for effective antibiotic management and sustainable shrimp production.