Exposure to high altitudes presents considerable challenges due to the reduced availability of oxygen, which may lead to conditions such as acute mountain sickness (AMS), high-altitude pulmonary edema (HAPE), and high-altitude cerebral edema (HACE). This chapter investigates the diagnostic and therapeutic potential of microRNAs (miRNAs) in mitigating high-altitude-related maladies. It underscores the critical role of miRNAs, particularly miR-210 and miR-21, in hypoxia-induced mechanisms such as angiogenesis and inflammation, which are vital for physiological adaptation to elevated altitudes. The discussion encompasses the mechanisms underlying miRNA regulation, their application as noninvasive biomarkers, and the development of novel therapeutic approaches such as miRNA mimics and inhibitors. By integrating recent empirical findings, this chapter illustrates the ability of microRNAs (miRNAs) to support the advancement of personalized medicine and improve health outcomes for individuals subjected to high-altitude conditions.