Holistic imaging of diverse functional, anatomical, and molecular architecture that span multiple levels, from cells to an entire system, remains a major challenge in biology. In this talk, I will introduce a series of technologies that enable integrated multiscale imaging and molecular phenotyping of both animal tissues and human clinical samples. I will discuss how we engineer (1) the physicochemical properties of biological tissues, (2) molecular interactions, and (3) molecular transport all together to achieve integrated organ-wide 3D molecular analysis at unprecedented speed and resolution. I will also discuss how these technologies can be commercialized and deployed synergistically to study a broad range of biological questions.