The introduced striped catfish (Pangasianodon hypophthalmus, Sauvage, 1878) and North African catfish (Clarias gariepinus, Burchell, 1822) are popular choices in Indian aquaculture due to their high productivity and ease of management. Among all introduced non-native fish species, catfish production is particularly notable, with P. hypophthalmus contributing 1.6 million metric tons (mmt) and C. gariepinus reaching 0.4 mmt. This paper examines the ecological, biodiversity, environmental, and disease concerns associated with the intensive aquaculture of the non-native catfish species, using a OneHealth approach to assess sustainability. Generated information on biological plasticity, resource competition, genetic interactions, invasion risks, biodiversity impacts, food safety, and disease risks in extensive aquaculture of non-native catfish are presented. A risk assessment (RA) was performed using an Excel-based developed module having 28 attributes and rated on a scale of 1 to 5. The results indicated significant risks, particularly for C. gariepinus, which had a risk score of 116 out of total 140 response points obtained from 65 farmers, manifesting 82.85% risk. In comparison, P. hypophthalmus had a response score of 85, displaying 60.71% risk. The findings suggest that C. gariepinus poses a higher ecological risk than P. hypophthalmus, primarily due to poorly controlled aquaculture practices, inadequate biosecurity, and insufficient regulatory measures. To tackle these issues, it is recommended that stringent policy with clear regulatory framework on the OneHealth approach will ascertain safe interconnectedness of aquaculture, environment, fish, and human health while improving the biosafety of non-native catfish aquaculture practices safeguarding human health, fish populations, and overall ecosystem health.