Background <p>The treatment of drug-resistant tuberculosis (DR-TB) is complex, longer, and it is associated with adverse drug reactions, contributing to higher morbidity and mortality rates. DR-TB presents a serious public health challenge, particularly in low- and middle-income countries where the burden is highest. We assessed DR-TB success rates and associated factors in Tanzania.</p> Methods <p>We collected data from DR-TB national data base and analyzed final treatment outcomes of 1,998 DR-TB patients registered for the six years (2017–2022) contributing 69% of the total DR-TB patients started on treatment in Tanzania since 2009. Factors associated with treatment outcomes were determined through multivariable analysis using logistic regression.</p> Results <p>The overall treatment success rate for DR-TB was 80% (<i>n</i> = 1,594). Factors influencing treatment success included age, nutritional status, HIV serostatus, and specific treatment regimens. Patients aged 15–29 years had a significantly higher likelihood of treatment success (aOR: 1.83, 95% CI: 1.26–2.64). Normal nutritional status at baseline was associated with higher treatment success (aOR: 4.14, 95% CI: 3.01–5.68), as was HIV-negative status (aOR: 1.51, 95% CI: 1.16–1.95). Specific regimens such as Standard Short Regimen (S-SCR) and All Oral Modified Shorter Regimen (AOSR) were significantly associated with higher treatment success (aORs: 1.62, 95% CI: 1.12–2.36 and 2.37, 95% CI: 1.43–3.90, respectively).</p> Conclusion <p>The study highlights that younger age groups, normal nutritional status, HIV-negative status, and specific treatment regimens like S-SCR and AOSR are significant influencing factors of DR-TB treatment success. To improve DR-TB treatment success rates the national TB program in Tanzania could prioritize the use of S-SCR and AOSR regimens, ensure a good nutritional status at baseline and appropriate management of HIV co infected DR-TB patients.</p> Clinical trial <p>Not applicable.</p>