Cities are in need of radical knowledge system innovations and designs in the age of the Anthropocene. Cities are complex sites of interactions across social, ecological, and technological dimensions. Cities are also experiencing rapidly changing and intractable environmental conditions. Given uncertain and incomplete knowledge of both future environmental conditions and the outcomes of urban resilience efforts, today’s knowledge systems are unequipped to generate the knowledge and wisdom needed to act. As such, cities must modernize the knowledge infrastructure underpinning today’s complex urban systems. The principal objective of this dissertation is to make the case for, and guide, the vital knowledge system innovations that coastal cities need in order to build more resilient urban futures. Chapter 2 demonstrates the use of knowledge systems analysis as a tool to stress-test and upgrade the Federal Emergency Management Agency flood mapping knowledge system that drives flood resilience planning and decision-making in New York City. In Chapter 3, a conceptual framework is constructed for the design and analysis of knowledge co-production by integrating concepts across the co-production and urban social-ecological-technological systems literatures. In Chapter 4, the conceptual framework is used to analyze two case studies of knowledge co-production in the Miami Metropolitan Area to better inform decisions for how and when to employ co-production as a tool to achieve sustainability and resilience outcomes. In Chapter 5, six propositions are presented – derived from a synthesis of the literature and the three empirical cases – that knowledge professionals can employ to create, facilitate, and scale up knowledge system innovations: flatten knowledge hierarchies; create plural and positive visions of the future; construct knowledge co-production to achieve desired outcomes; acknowledge and anticipate the influence of power and authority; build anticipatory capacities to act under deep uncertainty; and identify and invest in knowledge innovations. While these six propositions apply to the context of coastal cities and flood resilience, most can also be useful to facilitate knowledge innovations to adapt to other complex and intractable environmental problems. Cities must move swiftly to create and catalyze knowledge system innovations given the scale of climate impacts and rapidly changing environmental conditions.