Purpose <p>To clarify the specific mechanism underlying the effect of running in a plateau hypoxic environment (PHE) on autonomic nervous system (ANS) function, address the limitations of existing single-dimensional and interdisciplinary research in current studies, and provide new insights into the regulatory role of ANS in plateau adaptation.</p> Methods <p>A comprehensive review was conducted across five dimensions: an overview of ANS physiology; the physiological effects of PHE on the human body; specific mechanisms by which running under PHE modulates ANS function; comparative analysis of running in PHE versus other training modalities; and prospects for future research.</p> Results <p>Running in PHEs triggers a continuous ANS response, transitioning from mild activation under moderate intensity or altitude, to acute sympathetic dominance at higher intensities or altitudes, and finally to parasympathetic rebalancing during chronic exposure or training. This adaptive process enhances cardiopulmonary function, optimizes oxygen transport efficiency, and increases lactate tolerance, thereby improving aerobic metabolic capacity, hypoxia tolerance, and running economy in athletes. Compared with high-intensity hypoxic–low-altitude training and intermittent hypoxic training, running in PHEs offers unique advantages in maximizing physiological potential, though its application is constrained due to geographical accessibility.</p> Conclusion <p>The ANS plays a central regulatory role in human adaptation to running in PHEs. This study systematically clarifies the adaptive mechanisms and athletic performance-enhancing effects of such exercise, establishes a theoretical foundation for subsequent research on plateau training and ANS regulation, and highlights directions for developing personalized training programs and advancing technological innovation.</p>