Abstract Objective: Drug-resistant tuberculosis remains a major public health challenge in Indonesia. This study aimed to characterize the genetic diversity, lineage distribution, and genotypic resistance profiles of Mycobacterium tuberculosis isolates across the Indonesian archipelago using whole-genome sequencing. Methods: A cross-sectional study was conducted using 1,281 analyzed MTB isolates derived from the 2017–2018 National Tuberculosis Drug Resistance Survey (DRS TB).