Multidrug-resistant tuberculosis (MDR-TB) remains a global public health challenge. We aimed to investigate the utility of combining the cardiometabolic index (CMI) and systemic inflammation response index (SIRI) as biomarkers for rapid MDR-TB screening. Data were collected from 2,620 TB patients in Zibo city from 2018 to 2021. Logistic regression and receiver operating characteristic (ROC) curve analyses were used to evaluate the associations and diagnostic performance of CMI and SIRI with MDR-TB. The prevalence of MDR-TB was 5.0% in new TB patients and 20.5% in recurrent TB patients. Both CMI and SIRI were significantly associated with MDR-TB in all models (
P
< 0.05). In new TB patients, the area under the curve (AUC) values of the ROC curves for SIRI, CMI, and their combination were 0.845, 0.806, and 0.910, respectively. In recurrent TB patients, the AUC values were 0.730, 0.875, and 0.902, respectively. The optimal cut-off points for SIRI and CMI were 0.72 and 1.81 in new TB patients, and 1.05 and 1.48 in recurrent TB patients, respectively. In conclusion, combining CMI and SIRI shows promise as a low-invasive, cost-effective tool for early MDR-TB screening, warranting further validation in diverse populations and TB subtypes.