In anticipation of a major transformation in healthcare, this review provides highlights that anticipate the near future for oral public health (and beyond). Personalized or precision healthcare reflects the expectation that advances in genomics, imaging, and other domains will extend our risk assessment, diagnostic, and prognostic capabilities, and enables more effective prevention and therapeutic options for all Americans. Meanwhile, the current healthcare system does not meet cost, access, or quality criteria for all Americans. It is now an imperative that the success of “smart,” quality, and cost‐effective high definition precision healthcare requires a public health perspective for several reasons: a) to enhance generalizability, b) to assess methods of implementation, and c) to focus on both risk and prevention in large and small populations, thereby providing a balance between the generation of long‐term knowledge and short‐term health gains. Sensitivity and resolution, reasonable cost, access to all Americans, coordinated comprehensive care, and advances in whole genome sequencing (WGS) and big data analyses, coupled to other advances in biotechnology and digital/artificial intelligence/machine learning devices, and the behavioral, social, and environmental sciences, offer remarkable opportunities to improve the health and wellness of the American people [genotype + phenotype + environment + behavior = high definition healthcare]. The opportunity is to significantly improve the well‐being and life expectancy of all people across the lifespan including the least‐advantaged people in our society and potentially increase access, reduce the national costs, and improve health outcomes.