<p>High-altitude environments present unique challenges for human physiology, particularly in Andean populations, where approximately 18 million people reside above 2,500 m in South America alone. These populations face not only the physiological stress of hypoxia but also socio-demographic challenges, including poverty, malnutrition, and limited access to protein-rich diets. Hypoxia at high altitudes, coupled with these socioeconomic factors, negatively impacts cognitive development, especially in children. The brain's high oxygen demand makes it particularly vulnerable to the effects of reduced oxygen availability, resulting in impaired cognitive functions such as memory, attention, and decision-making. Prolonged exposure to hypoxia can lead to structural changes in the brain, including alterations in white matter, neuronal damage, and compromised cerebrovascular regulation. In addition to hypoxia, malnutrition—especially the limited availability of vital nutrients—further exacerbates cognitive deficits in these populations. While Andean populations have developed physiological adaptations to mitigate some of these effects, such as increased vascularization and erythrocytosis, the combination of environmental and nutritional stressors continues to challenge cognitive health. This perspective explores the complex interaction between hypoxia, nutrition, and cognitive development in Andean high-altitude populations, discussing current findings and proposing future research directions to better understand these multifaceted challenges. It also compares adaptation strategies across highland populations and highlights the need for culturally contextualized and interdisciplinary approaches to guide future research.</p>