Ayurveda, an ancient Indian system of medicine documented and practised since 1500 B.C., follows a systems approach thathas interesting parallels with contemporary personalized genomic medicine approaches to the understanding and managementof health and disease. It is based on the trisutra, which are the three aspects of causes, features and therapeutics that areinterconnected through a common organizing principle termed ‘tridosha’. Tridosha comprise three ascertainable physiologicalentities; vata (kinetic), pitta (metabolic) and kapha (potential) that are pervasive across systems, work in conjunction witheach other, respond to the external environment and maintain homeostasis. Each individual is born with a specific proportionof tridosha that are not only genetically determined but also influenced by the environment during foetal development.Jointly they determine a person’s basic constitution, which is termed their ‘prakriti’. Development and progression of differentdiseases with their subtypes are thought to depend on the origin and mechanism of perturbation of the doshas, andthe aim of therapeutic practice is to ensure that the doshas retain their homeostatic state. Similarly, western systems biologyepitomized by translational P4 medicine envisages the integration of multiscalar genetic, cellular, physiological and environmentalnetworks to predict phenotypic outcomes of perturbations. In this perspective article, we aim to outline the shape ofa unifying scaffold that may allow the two intellectual traditions to enhance one another. Specifically, we illustrate how aunique integrative ‘Ayurgenomics’ approach can be used to integrate the trisutra concept of Ayurveda with genomics. Weobserve biochemical and molecular correlates of prakriti and show how these differ significantly in processes that are linkedto intermediate patho-phenotypes, known to take different course in diseases. We also observe a significant enrichment of thehighly connected hub genes which could explain differences in prakriti, focussing on EGLN1, a key oxygen sensor that differsbetween prakriti types and is linked to high altitude adaptation. Integrating our observation with the current literature,we demonstrate how EGLN1 could qualify as a molecular equivalent of tridosha that can modulate different phenotypic outcomes,where hypoxia is a cause or a consequence both during health and diseased states. Our studies affirm that integrationof the trisutra framework through Ayurgenomics can guide the identification of predisposed groups of individuals and enablediscovery of actionable therapeutic points in an individualized manner.