Pyopneumothorax is a rare complication of pulmonary tuberculosis, contributing significantly to morbidity and mortality. Additionally, factor XIII deficiency, a rare bleeding disorder, may pose a diagnostic challenge due to normal results in routine coagulation tests. We present the case of an 18-year-old boy who presented with a history of left-sided pyopneumothorax secondary to drug-sensitive Mycobacterium tuberculosis, complicated by congenital factor XIII deficiency. After three months of intercostal drainage placement, the patient developed severe anemia and bleeding tendencies, necessitating a referral to clinical hematology. Genetic testing revealed factor XIII deficiency. This case highlights the complicated interplay between tuberculosis-related complications and a coexisting genetic disorder, highlighting the importance of comprehensive clinical assessment and multidisciplinary management.