The influence of the built environment on our health and well-being is finally getting much deserved attention, eliciting a growing awareness and creating a paradigm shift in design approaches. With a growing demand for evidence of building performance, there is an urgent need to develop the science and design knowledge that will enable architects, engineers, and developers to accurately predict overall performance of buildings and their impact on the triple bottom line of people, planet, and profit. The building physical performance can be easily validated with state-of-the-art research, testing, and design guidelines but no matter how advanced building technology is, if architects and engineers do not understand how people engage with buildings to enrich their sensory and health outcomes while reducing energy use, we will continue to face short falls of design predictions and environmental déjà vu’s. This presentation will highlight on-going research projects from the High Performance Environments Laboratory (HiPE) at the University of Oregon and outline key considerations in developing a systemic approach to evidence-based design guidelines for the future.