Humans have successfully adapted to various terrains across the planet due to their robust homeostatic mechanisms. However, high-altitude environments remain an extreme challenge. The acclimatization process at high altitudes involves physiological adaptations such as hyperventilation, accelerated erythropoiesis, increased heart rate, and enhanced cerebral blood flow. These changes, while essential for survival, can disrupt normal brain functions. Cognitive function, critical for effective survival, encompasses the processes of gathering, processing, and acting upon environmental information. Impairments in cognitive function at high altitudes can pose serious risks, particularly for mountaineers and soldiers operating in these environments. Currently, resources to enhance cognition under such conditions are limited. Emerging research has identified mechanisms such as oxidative stress (reactive oxygen species), blood–brain barrier disruptions, microvascular damage, impaired autoregulation, altered neurotransmitter dynamics, and inflammatory cytokines as key factors contributing to cognitive decline at high altitudes. While various tools are available for assessing cognitive function—including neuropsychological tests (e.g., Cambridge Neuropsychological Test Automated Battery), questionnaire-based scoring, electrophysiological markers (e.g., event-related potential P300, contingent negative variance), fMRI, and molecular assessments of neurotransmitters and cytokines—wearable technologies for real-time cognitive monitoring remain underdeveloped. Effective acclimatization remains the most reliable strategy to enhance cognitive performance at high altitudes. Pharmacological interventions such as acetazolamide and dexamethasone, nutraceuticals like quercetin and curcumin, and non-pharmacological measures, including supplemental oxygen, have proven to support acclimatization and cognitive function.