<p>Lung cancer is a leading cause of cancer-related morbidity and mortality worldwide. Diabetes, as a common metabolic disorder, further increases the risk of cardiovascular damage. Studies have shown that myocardial cells in diabetic patients are more vulnerable to the toxic effects of cancer treatments, thereby raising the risk of heart failure. Therefore, cardiovascular risk assessment in lung cancer patients with diabetes is particularly important. The Inflammatory Burden Index (IBI) is a biomarker that reflects systemic inflammation, combining the levels of C-reactive protein (CRP), neutrophils, and lymphocytes. It has been shown to be a significant prognostic indicator in various cancer populations. This study aims to investigate the predictive ability of IBI and the triglyceride-glucose (TyG) index for cardiac injury in lung cancer patients with diabetes undergoing antitumor therapy. A single-center retrospective case-control study was conducted, including clinical data of 192 lung cancer patients with diabetes who received anti-tumor therapy from July 2018 to January 2023.Cardiac injury was assessed by measuring high-sensitivity cardiac troponin T (hs-cTnT) levels. The Inflammatory Burden Index (IBI) was calculated using the formula: IBI = (C-reactive protein [CRP] × Neutrophils)/Lymphocytes. Univariate and multivariate logistic regression analyses were performed to assess the relationship between clinical factors, IBI, TyG index, and cardiac injury. The clinical predictive value of these factors was further evaluated using receiver operating characteristic (ROC) curves, and the relationship between IBI and cardiac injury was explored using the Restricted Cubic Spline (RCS) model. In the 192 patients, 101 (52.6%) developed cardiac injury during follow-up. Univariate analysis showed that age, male, hypertension, smoking, D-dimer, CKMB, IBI, TNM stage: III/IV, and Immunotherapy were significantly associated with cardiac injury (<i>P</i> &lt; 0.001). Multivariate analysis identified IBI (<i>P</i> = 0.007), age (<i>P</i> = 0.01), smoking (<i>P</i> &lt; 0.001), CKMB (<i>P</i> &lt; 0.001), TNM stage (<i>P</i> = 0.014), and hypertension (<i>P</i> = 0.007) as independent predictors of cardiac injury. ROC analysis revealed an area under curve (AUC) of 0.722 for IBI (cut-off: 8.408), indicating good predictive value. RCS analysis showed a significant nonlinear positive correlation between IBI and cardiac injury (<i>P</i> = 0.0079), with the risk of cardiac injury increasing significantly as IBI levels rose. The TyG index was not significantly associated with cardiac injury. IBI, as a simple and accessible biomarker, can effectively predict cardiac injury in lung cancer patients with diabetes undergoing antitumor therapy. Although the TyG index did not show a significant association with cardiac injury in this study, IBI demonstrated strong predictive ability in this patient group. Future studies should further validate the use of IBI across different cancer types and evaluate its prognostic role in long-term follow-up.</p>