Sustainability science is use-inspired fundamental research that links knowledge to action such that meeting the needs of society can be balanced with sustaining the life support systems of the planet (1, 2). Nowhere is this action-oriented research needed more than in urban areas that are now home to more than half of the world's population, generating about 80% of the world's economy (3) as well as over 70% of global energy use and global energy-related emissions (4). Depending on the literature and perspectives taken, urbanization and cities will be either key components to the transition to sustainability or major threats to sustainability. The dichotomy in views is partly a result of the wide range in urban conditions and uneven urbanization processes around the world. Urban areas can be sites of innovation and production of knowledge and wealth, and provide widespread access to employment, education, sanitation, and modern energy, but they can also have high levels of pollution, social exclusion, environmental degradation, and cause unintended consequences outside of the urban boundaries; all of these outcomes could occur simultaneously through the same urbanization process.A number of urban transitions are underway, several of which involve: the change from a predominantly rural and lower-density population to an urban and higherdensity living; the shift in economies from agrarian to manufacturing and services, finance, and technology; the increasing resource intensity of energy, materials, and water required to produce a unit of good or service; the lasting imprint and spatial configuration of built environments and their requisite infrastructures; the subtle impact on a broad spectrum of biotic interactions and the significant threats to biodiversity; the increasing complexity and reach of urban institutions and governance to enforce the rule of law and maintain civil society; and the transition from individually demarcated cities and towns to the emergence of mega-urban regions, which are extended metropolitan areas that encompass multiple urban centers and are larger in size than mega-cities.The simultaneity of these transitions, combined with the scale of mega-urban regions and the expanding geographic reach of urban processes, signals a significant break in human-environment interactions, from local or regional scale to global consequences. It is important to underscore that these large-scale changes are occurring contemporaneously in hundreds of urban areas around the world, and not just in a few locations. Indeed, what was once considered exceptional-large-scale and rapid urbanization-is now the norm in many places. The scale of mega-urban regions is notable in two key dimensions: (i) the number and concurrent development of them worldwide; and (ii) their physical extent and population size: the Boston-Washington corridor is home to 18% of the United States population; the Pearl River Delta in China has a population of about 120 million; the TokyoYokohama region in Japan covers about 13,500 km 2 ,...