The coexistence of heavy metals and pesticides poses a critical challenge in agricultural ecosystems. Traditional toxicity assessments often focus only on the individual impacts of either pesticides or heavy metals. Here, the untargeted metabolomics and 16 S rRNA sequencing were used to assess the individual and combined effects of cadmium (Cd) and triazophos (TRI) on hook snout carps (Opsariichthys bidens). Cd caused much more serious impacts on hepatic metabolism and gut microbiota than those in TRI. Combined Cd and TRI exposure synergistically affected hepatic metabolism, causing mitochondrial dysfunction and even oxidative damage. Simultaneously, 16 S rRNA sequencing highlighted significant variations in the composition and abundance of gut microbiota. A noteworthy connection emerged between these distinct microbiota profiles and disruptions in energy metabolism, ultimately leading to disorders in metabolites. These findings enhanced the understanding of risks posed by heavy metals and pesticides, providing insights for better environmental risk assessments of aquatic organisms.