Background: Tuberculosis remains a major public health concern in China, with varying prevalence and drug resistance profiles across regions. This study explores the genetic diversity and drug-resistant profiles of MTB strains in Hinggan League, a high TB Methods: This population-based retrospective study, encompassing all culture-positive TB cases from Jun. 2021 to Jun. 2023 in Hinggan League. Drug resistant profiles and genetic diversity of MTB strains were assessed using phenotypic drug susceptibility testing and whole-genome sequencing. Risk factors associated with drug resistance were analyzed using univariate and multivariate Results: A total of 211 MTB strains were recovered successfully and included into final analysis. Lineage 2.2.1 (88.6%, 187/211) was the dominant sub-lineage, followed by lineage 4.5 (7.1%, 15/211) and lineage 4.4 (4.3%, 9/211). MTB strains exhibited the highest resistance rates to isoniazid (16.1%, 34/211), followed by rifampicin (10.0, 21/211). In addition, the MTB strains also showed relatively high rates of resistance against new and repurposed anti-TB drugs, with resistant rates of 2.4% (5/211) to delamanid and 1.9% (4/211) to bedaquiline. Overall, 25.6% (54/211) of MTB strains were DR-TB, and 14 MTB strains met the definition of MDRTB, including 7 strains of simple-MDR-TB, 5 of pre-XDR-TB, and 2 of XDR-TB. Genetic analysis revealed that the dominant mutations of isoniazid-, rifampin-, ethambutol-, levofloxacin-/moxifloxacin-, and ethionamide- resistance were katG_Ser315Thr (46.4%), rpoB_Ser450Leu (47.4%), embB_Met306Val (25.0%), gyrA_Asp94Ala (40.0%), and fabG1_c15t (42.9%), respectively. Previously treated patients (AOR = 2.015, 95% CI: 1.052-4.210) and male patients (AOR = 3.858, 95% CI: 1.416-10.511) were Conclusion: Our study offers crucial insights into the genetic diversity and drug-resistant profiles of TB strains circulating in Hinggan League. These findings are valuable for DR-TB surveillance and for guiding treatment regimens and public health interventions in the region.