Abstract Objectives Multidrug-resistant tuberculosis (MDR-TB) has become a major global public health issue, which has worsened over time owing to changes in disease-related trends. This study aimed to determine global trends in MDR-TB among children and adolescents for strategic health planning. Methods A secondary analysis was performed on MDR-TB burden among children and adolescents (<20 years) at the global, regional, and national levels based on sociodemographic index (SDI) quintiles from 1990 to 2019, using the Global Burden of Disease (GBD) 2019 database. Results In 2019, 67,710.82 (95% uncertainty interval [UI]: 38,823.61 to 110,582.03) incidents of MDR-TB were reported among children and adolescents aged <20 years worldwide. The global incidence rate has increased from 1990 to 2019, with the estimated annual percentage change (EAPC) at 4.15% (95% UI: 1.10–12.19%), particularly in low- and low-middle SDI regions. The top three highest incidence rates were observed in Southern sub-Saharan Africa, Eastern Europe, and South Asia. The mortality and disability-adjusted life years (DALYs) rates (0.62 [95% UI: 0.28–1.14] and 55.19 [95% UI: 25.24–100.74] cases per 100,000, respectively) were higher among children aged <5 years than those in older age groups in 2019. Conclusion The global burden of MDR-TB among children and adolescents has increased from 1990 to 2019, particularly in regions with lower SDI. Extensive collaborative research and interventions are needed to mitigate this disease burden to secure the health of our future generation. Impact MDR-TB disease burden in children and adolescents using GBD 2019 database was analyzed. In total, 67710.82 MDR-TB cases were identified in children and adolescents in 2019. Global MDR-TB burden in children and adolescents has risen over the past 30 years. MDR-TB disease burden is negatively correlated with the sociodemographic index. MDR-TB disease burden varies across countries and age groups.