Langerhans cell histiocytosis is a rare condition characterized by aberrant function and proliferation of the mononuclear phagocyte system. It can occur across all age ranges. This case report involves an adult female presenting with multisystem involvement and pleural effusion. A hypothesis suggests that chronic inflammatory states, resulting from cytokine production and the release of proinflammatory factors, alter vascular permeability, potentially leading to clinical manifestations such as fluid distribution abnormalities, including pleural effusion. Symptomatic multisystemic disease requires chemotherapy initiation. In this case, treatment could not be started due to unresolved empyema despite surgical intervention.