We will conduct a single-site observational cohort study of 210 adult participants with pulmonary smear-positive, rifampin-resistant TB to systematically evaluate the impact of a combination Baseline pRescription According to Direct from Sputum Sequencing and TArgeted drug Concentration Strategy (BRASS TACS) for personalized MDR-TB therapy as access to these tools expands. The specific aims of this proposal are to: 1) determine the proportion of patients with MDR-TB in Mumbai, India with resistance-associated mutations that would prevent treatment with moxifloxacin, linezolid, bedaquiline, clofazimine, or cycloserine using culture-free next generation sequencing (NGS); 2) identify the proportion of cohort participants with MDR-TB that achieve model-derived steady-state plasma levels meeting efficacy and toxicity targets; and 3) assess the time to final regimen, frequency of treatment-associated side effects, time to culture conversion, and final outcome of cohort participants who complete culture-free NGS and TDM. The results of this observational cohort will determine the combined benefit of these tools as they are deployed at a referral center with clinical and laboratory expertise in complex drug resistance. These data will describe the real-world outcomes of MDR-TB care using NGS and TDM for MDR-TB in a unique setting and will inform the future application of these tools to improved strategies for personalized MDR-TB treatment worldwide.