Buildings kill an estimated 1 billion songbirds each year in the United States alone. Apart from the heartbreaking destruction of beautiful, innocent life, this catastrophic loss of biodiversity represents a public health emergency that tragically illuminates an all too literal clash between nature and culture. If evolution is any guide, culture must urgently realign with the biology of life. As the pervasiveness of human inflammatory conditions suggests, our hard-edged glass, steel, and concrete-dominated environments do not support our own biology either. In addition to biodiversity loss, chronic stress from extreme heat, noise, light, and air pollution degrades public health and well-being in many of our neighborhoods. From anxiety and loneliness to dementia, from hypertension to cancer, daily stress conditions corrode our immune response, reduce productivity, and fray our social fabric. The problem illuminates a science-informed path from opportunity to obligation: all buildings, new and existing, must adapt to become restorative, transformative, nature and body-positive infrastructure investments in public health. Local ecology must become intrinsic to each ecotonal building-envelope’s design, supporting physiological well-being by mitigating air, noise, and light pollution, naturally cooling interiors and surrounding neighborhoods, sequestering carbon, and fostering urban micro-habitat biodiversity in symbiotic realignment with the biology of all urban lives.