Medical sciences have always shown keen interest in studying the interaction between cardiopulmonary health and high-altitude environments. One such condition that arises under extreme environmental conditions, significantly affecting human cardiovascular and pulmonary systems, is hypobaric hypoxia. At high altitudes, individuals undergo physiological acclimatization, such as increased ventilation, shifts in fluid regulation, elevated heart rates, and vascular adaptations. These conditions result in hypertension, high-altitude pulmonary edema, ischemic heart disease, and heart failure. The present chapter aims to explore unresolved issues concerning the interface between cardiopulmonary diseases and high altitude. The primary focus areas include environmental variables faced at high altitude, cardiopulmonary pathophysiology, possible influencing factors, and treatments available for managing these health conditions that ultimately result in hypobaric hypoxia-induced illnesses. Through filling these knowledge voids, prospective practitioners can gain a deeper understanding of how to reduce the risks associated with high-altitude exposure in susceptible demographics, ultimately improving their quality of life during altitude-related pursuits.