With millions of interacting people and hundreds of governing agencies, urban environments are the largest, most dynamic, and most complex macroscopic systems on Earth. All of that complexity can be boiled down to interactions between the three fundamental components of cities: the human, natural, and built environments. I will describe how persistent, synoptic imaging of an urban skyline at visible and infrared wavelengths can be used to better understand the urban system and how we at the Urban Observatory – a multi-institutional facility designed to study complex urban systems – are combining techniques from the domains of astronomy, physics, engineering, computer vision, remote sensing, and machine learning to address a myriad of questions related to urban informatics and its implications for evidenced-based policy making. I will show how this data from the Urban Observatory can provide new insights into cities as living organisms that consume energy, have environmental impact, and display characteristic patterns of life and how that new understanding can be used to improve city functioning and quality of life for its inhabitants.