Cadmium accumulation in seafood has become a major concern for human health. Recently, there has been an increasing focus on the potential risks associated with food-borne fluorescent carbon dots (CDs) that are formed during the thermal processing of seafood. The co-occurrence of cadmium and CDs from cooked seafood become a common phenomenon and co-exposure of them to human has been an inevitable route during long-term seafood consuming. In addition, it has been widely recognized that CDs can be used as nanocarriers for metal ion chelation for their transport into organisms, thereby, they could influence the bioavailability of metal ion. While there have been numerous studies on the toxic effects of cadmium or CDs, none have explored the combined toxicity of food-borne CDs from clams (CCDs) and Cd2+. In this study, we investigated the single or co-exposure (combined exposure) of Cd2+ and CCDs on PC12 cells to investigate the combined toxicity of them. Our analysis of cell viability revealed that CCDs significantly augmented the cytotoxicity induced by Cd2+ . More in-depth metabolomics and lipidomics investigation indicated that the combined exposure of Cd2+ and CCDs led to significant metabolic disorders, causing an antagonistic effect on energy metabolism, and a synergistic effect on amino acids and lipids metabolism. The disturbance in metabolomics and lipidomics was further supported by the disruption of mitochondrial membrane potential and the accumulation of reactive oxygen species following co-exposure. These findings provide new evidence that support the enhanced cytotoxicity of Cd2+ by the CCDs derived from the thermal processing of clams. This study also declares the necessary that prioritize the investigation of the potential impact of other thermal processing hazards originating from heat-processed foods on the toxicity of heavy metal ions.