This case report presents a rare instance of concomitant splenic tuberculosis (TB), Epstein–Barr virus (EBV)-related T-cell leukemia/lymphoma, and malaria in a 28-year-old pregnant woman at a Médecins Sans Frontières-supported hospital in South Sudan. The patient was admitted with splenomegaly, anorexia, weakness, and transfusion-refractory anemia. She tested positive for malaria and was treated appropriately. Because of ongoing consumptive anemia, cachexia, and weakness severely impacting her quality of life, the patient underwent splenectomy. A diagnosis of TB was ultimately confirmed post-splenectomy through histopathological analysis and molecular testing. Gross findings from the pathologic analysis of a splenic sample revealed miliary deposits, necrotizing granulomas, and atypical lymphocytic infiltrates consistent with TB and EBV-associated leukemia/lymphoma. Despite temporary improvement post-operatively and the initiation of TB therapy, the patient discontinued treatment and was lost to follow-up, likely resulting in mortality. This report presents an unusual combination of concomitant pathologies that underscore the diagnostic challenges and complexity of managing overlapping infectious and hematological disorders in resource-limited settings.