Never in history have we built so much, in so many different places. Population growth, urbanization, and technological change are all pushing us to conceive and design spaces in human societies in new and better ways, aiming toward more environmentally sustainable and socially equitable human settlements. Much of what is happening in the fastest-growing cities in the world today, however, is informal; while vital, this development fails to incorporate advanced knowledge or seize opportunities for leapfrogging solutions. I discuss these challenges from the perspective of what we know scientifically about cities and the formal processes of design in order to illustrate how spatial design enriched by new data and methods of analysis can fulfill its long-avowed aspirations to create open-ended complex systems that are an integral part of networked processes of sustainable human development.