There is a growing recognition that the built environment can substantially impact occupant well-being. However, pinpointing the specific impacts of design features proves to be challenging. While significant advancements have been made using sensing, feedback, and control in " smart buildings”, outcomes have focused primarily on energy savings, temperature comfort, and security. Buildings of the future should go beyond this to infer and support the mental and physical well-being of the occupants. A scientific approach to designing buildings for wellbeing can both create knowledge as well as improve the physical and mental health of large populations. Our team with expertise in architecture, structural and materials engineering, human-computer interaction, psychology, environmental behavior, security, privacy, and law is examining how interior features (i.e., materials, lighting, and artwork representing diverse identities) relate to multifaceted dimensions of well-being. Through online studies and a large (N=412) controlled experiment we have been exploring the effects of these varied features on biopsychosocial indicators of well-being including belonging, stress, creativity, and pro-environmental concern, measured through physiological sensors and self-reported assessments. The results of these studies and their implications will be presented, as well as methodological challenges surrounding the design, experimentation, and operation of human-centered built environments.