In today’s globalized and flat world, a patient can access and seek multiple health and disease management options. A digitally enabled participatory framework that allows an evidence-based informed choice is likely to assume an immense importance in the future. In India, traditional knowledge systems, like Ayurveda, coexist with modern medicine. However, due to limited crosstalk between the clinicians of both disciplines, a patient attempts integrative medicine by seeking both options independently with limited understanding and evidence. There is a need for an integrative medicine platform with a formalized approach, which allows practitioners from the two diverse systems to crosstalk, coexist, and coevolve for an informed cross-referral that benefits the patients. To be successful, this needs frameworks that enable the bridging of disciplines through a common interface with shared ontologies. Ayurgenomics is an emerging discipline that explores the principles and practices of Ayurveda combined with genomics approaches for mainstream integration. The present review highlights how in conjunction with different disciplines and technologies this has provided frameworks for (1) the discovery of molecular correlates to build ontological links between the two systems, (2) the discovery of biomarkers and targets for early actionable interventions, (3) understanding molecular mechanisms of drug action from its usage perspective in Ayurveda with applications in repurposing, (4) understanding the network and P4 medicine perspective of Ayurveda through a common organizing principle, (5) non-invasive stratification of healthy and diseased individuals using a compendium of system-level phenotypes, and (6) developing evidence-based solutions for practice in integrative medicine settings. The concordance between the two contrasting streams has been built through extensive explorations and iterations of the concepts of Ayurveda and genomic observations using state-of-the-art technologies, computational approaches, and model system studies. These highlight the enormous potential of a trans-disciplinary approach in evolving solutions for personalized interventions in integrative medicine settings.