Although Group 5 PH represents less-explored manifestations of PH, it accounts for a significant portion of the global PH burden. It comprises hematological disorders (e.g., sickle cell disease and chronic myeloproliferative neoplasms), systemic conditions such as sarcoidosis, metabolic diseases such as glycogen storage disease, and other conditions including chronic renal failure, pulmonary tumor thrombotic microangiopathy, and fibrosing mediastinitis. A common characteristic of these diseases is the limited understanding of the mechanisms underlying PH, with potential contributing factors including hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, thrombosis, fibrotic damage and/or external compression of the pulmonary vasculature, and vasculitis. The treatment should be tailored to address the underlying condition.