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Objectives This study aimed to evaluate the cost-effectiveness of integrating nutritional support into India’s National Tuberculosis Elimination Programme (NTEP) using the MUKTI initiative.Design Economic evaluation.Setting Primary data on the cost of delivering healthcare services, out-of-pocket expenditure and health-related quality of life among patients with tuberculosis (TB) were collected from Dhar district of Madhya Pradesh, India.Intervention Integration of nutritional support (MUKTI initiative) into the NTEP of India.Control Routine standard of care in the NTEP of India.Primary outcome measure Incremental cost per quality-adjusted life year (QALY) gained.Methods A mathematical model, combining a Markov model and a compartmental susceptible–infected–recovered model, was used to simulate outcomes for patients with pulmonary TB under NTEP and MUKTI protocols. Primary data collected from 2615 patients with TB, supplemented with estimates from published literature, were used to model progression of disease, treatment outcomes and community transmission dynamics over a 2-year time horizon. Health-related quality of life was assessed using the EuroQol 5-Dimension 5-Level scale. Costs to the health system and out-of-pocket expenditures were included. A multivariable probabilistic sensitivity analysis was undertaken to estimate the effect of joint parameter uncertainty. A scenario analysis explored outcomes without considering community transmission. Results are presented based on health-system and abridged societal perspectives.Results Over 2 years, patients in the NTEP plus MUKTI programme had higher life years (1.693 vs 1.622) and QALYs (1.357 vs 1.294) than those in NTEP alone, with increased health system costs (₹11 538 vs ₹6807 (US$139 vs US$82)). Incremental cost per life year gained and QALY gained were ₹67 164 (US$809) and ₹76 306 (US$919), respectively. At the per capita gross domestic product threshold of ₹161 500 (US$1946) for India, the MUKTI programme had a 99.9% probability of being cost-effective but exceeded the threshold when excluding community transmission.Conclusion The findings highlight the potential benefits of a cost-effective, holistic approach that addresses socio-economic determinants such as nutrition. Reduction in community transmission is the driver of cost-effectiveness of nutritional interventions in patients with TB.