Hypobaric hypoxia at high altitudes threatens the health of high-altitude residents. The development of effective methods to guarantee the safety of frequent human activities in high-altitude locations is therefore needed. Pre-acclimatization at sea level is an effective approach to mitigate subsequent altitude sickness for rapid ascent, which offers a viable substitute to on-site acclimatization, minimizes the associated risks that are linked to prolonged exposure in high-altitude environments and can be personalized to individual hypoxic responses. Another critical aspect to prevent long-term physical damage is personalized health management at high altitudes, which is enabled by the emerging technologies of wearable sensors, the Internet of Medical Things and artificial intelligence. In this review, we outline the progress in pre-acclimatization and high-altitude health management, as well as the understanding of physiological mechanisms under hypoxia, highlighting the important role that is played by wearable sensors and physiological closed-loop control systems in developing intelligent personalized solutions. We also discuss the challenges and prospects of deploying autonomous intelligent monitoring and control in high-altitude health management. This review introduces advancements in pre-acclimatization and health management at high altitudes, emphasizes the important role of wearable sensors and autonomous intelligent control in high-altitude healthcare, and proposes a promising personalized closed-loop control framework for oxygen saturation regulation.