<p>Drug-induced cardiotoxicity (DIC) poses a significant challenge in both drug development and clinical practice, Making early and accurate assessment crucial. Existing studies have shown that mitochondrial fusion mediated by mitochondrial fusion protein 2 (Mfn2) is closely associated with DIC, and that upregulation of Mfn2 reduces drug-induced cardiomyocyte damage and apoptosis, suggesting that Mfn2 could be a potential biomarker for early warning assessment of DIC. Due to the defects of cumbersome operation, limited sensitivity, high cost, and difficulty in popularization of existing detection technologies, this study pioneers a novel electrochemical immunosensor for highly sensitive Mfn2 detection using a composite sensing substrate of MXene-derived sodium titanate nanorods and multi-walled carbon nanotubes (M-NTO-MWCNT). This technology enables early warning and assessment of drug-induced cardiotoxicity. The M-NTO component, with its unique nanorod structure, abundant active sites, and high surface area, significantly enhances sensitivity and provides abundant antibody immobilization sites. Meanwhile, MWCNTs improve electron transfer efficiency and selectivity due to their superior conductivity and interconnected network. Under optimized conditions, the sensor achieves a detection Limit as low as 1.85&#xa0;ng&#xa0;mL⁻¹ and a Linear range of 9.38 × 10⁻¹–2.40 × 10²&#xa0;ng&#xa0;mL⁻¹. Serum sample testing demonstrated excellent reproducibility (RSD &lt; 5%), outperforming conventional ELISA methods. This study provides a new rapid and highly sensitive test solution for the early warning of drug-derived cardiotoxicity, offering technical support and scientific basis for safety assessment in new drug development.</p> Graphical Abstract <p></p>