Cage farming of Pangas catfish (Pangasionodon hypophthalmus) in small reservoirs is primarily profitable. Still, sustainability in terms of disease and environmental impact issues remains unsolved. In the present study, Pangas catfish from selected farms were screened for bacteria and parasites from 2017-18. In the present study, several Gram-negative bacterial species, including Edwardsiella tarda, Aeromonas hydrophila, A. veronii, Pseudomonas putida, Enterobacter cloacae, and Plesiomonas shigelloides, were isolated. A high prevalence of Aeromonas and Pseudomonas infections was noticed in cage farms. The most prevalent isolate was A. veronii (9 isolates), followed by P. aeruginosa and P. putida, revealing the presence of biotic stress.Furthermore, potential human pathogenic bacteria, particularly Klebsiella pneumoniae, P. aeruginosa, Acinetobacter baumannii, Citrobacter freundii, and Morganella morganii, were isolated. Histopathological analysis of the vital organs concluded the extent of damage caused due to the biotic stress in the cage culture system. The antibiotic sensitivity test implied resistance of bacteria for Sulphamethoxazole and Tetracycline. Some of them were resistant to multiple drugs, the risk for public health. Water temperature, dissolved oxygen, pH, Aeromonas, Pseudomonas, and Plesiomonas were identified by principal component analysis as significant abiotic and biotic stress factors. This information helps design predictive disease models.