Precision medicine (PM), through the integration of omics and environmental data, aims to provide a more precise prevention, diagnosis, and treatment of disease. Currently, PM is one of the emerging approaches in modern healthcare and public health, with wide implications for health care delivery, public health policy making formulation, and entrepreneurial endeavors. In spite of its growing popularity and the buzz surrounding it, PM is still in its nascent phase, facing considerable challenges that need to be addressed and resolved for it to attain the acclaim for which it strives. In this article, we discuss some of the current methodological pitfalls of PM, including the use of big data, and provide a perspective on how these challenges can be overcome by bringing PM closer to evidence-based medicine (EBM). Furthermore, to maximize the potential of PM, we present real-world illustrations of how EBM principles can be integrated into a PM approach.