Tuberculosis (TB) remains a major global health challenge, particularly in high-burden countries like India, where the incidence and mortality rates continue to pose significant public health concerns. Despite the availability of effective antitubercular therapy (ATT), adverse drug reactions (ADRs) such as antitubercular drug-induced liver injury (AT-DILI) remain a hindrance to the successful management of TB. AT-DILI could lead to hospitalisation, increased cost expenditures, treatment interruptions, suboptimal adherence, and poorer TB treatment outcomes, such as increased morbidities and mortality and longer treatment durations, necessitating a need for predictive biomarkers to stratify high-risk patients early, intensively monitor them for ADRs such as AT-DILI, and tailor their management strategies accordingly. The proposed study aims to address these critical knowledge gaps by integrating NAT2 pharmacogenomics and metabolomic approaches to develop a pre-emptive biomarker-based strategy for screening and early identification of AT-DILI. By conducting a non-randomized controlled trial (NRCT), the study aims to establish the most effective NAT2 genotype-guided liver function test (LFT) monitoring strategy for early AT-DILI detection and prevention. Furthermore, a longitudinal metabolomics analysis will be performed to identify novel metabolic signatures that can serve as pre-emptive biomarkers for AT-DILI and differentiate TB patients from healthy individuals. The phase-1 observational study will include TB patients with or without co-morbidities, along with healthy controls and type-2 DM patients (T2DM). Blood samples will be collected, and NAT2 genotyping will be carried out. Baseline metabolomic analysis will be performed in these TB patients, healthy controls and T2DM patients prior to initiation of therapy to identify alterations in the metabolomic signatures. Based on the NAT2 genotyping/phenotyping status, the TB patients will be grouped for NRCT into either NAT2 slow acetylators or NAT2 intermediate/rapid acetylators for DILI monitoring. These patients will be intensively monitored for liver function status for DILI at intervals of 1-, 2-, 4- and 8-weeks after initiation of the therapy. The patients with confirmed AT-DILI will receive adjusted INH dosing, followed which the patients will be assessed for the occurrence of AT-DILI. This study will provide proof-of-concept-based personalized medicine in TB care, offering a scalable model for pharmacogenomic and metabolomic biomarker-guided interventions in diverse TB populations.