Tuberculosis (TB) has become one of the global burdens of disease, with increasing morbidity and mortality every year. Tuberculosis can affect not only the lungs but also the extrapulmonary organs. The prevalence of drug-resistant tuberculosis (DR-TB) is rising and has caused a higher mortality rate than drug-susceptible tuberculosis (DS-TB). This article presents a patient with a rare co-infection of pulmonary DS-TB and pleural DR-TB. Pulmonary and pleural TB (pTB) was diagnosed using the Xpert MTB/RIF assay. The patient was treated with an individualized DR-TB regimen and recovered. © 2025, Indonesian Society of Internal Medicine. All rights reserved.