In an increasingly urbanized world, the concepts of ecosystem services and nature-based solutions can help tackle grand challenges. However, ambiguity in their definitions and in the relationship between the two concepts complicates comprehensive research efforts as well as their effective application in policy and planning in urban systems. This paper presents a framework to clarify and explicitly relate the two concepts, enhancing their applicability in the management of urban challenges. Within the framework, addressing urban challenges serves as the starting point for the development and implementation of nature-based solutions. Nature-based solutions alter the flows of ecosystem services that are produced by an ecosystem by altering the performance of the ecosystem or by changing how people engage with the ecosystem. This results both in changes in the target ecosystem services, as well as non-targeted ecosystem services, leading to benefits. Using two illustrative case studies, we show how the framework can be applied to two urban challenges that are expected to increase in intensity in cities across the world: stormwater management and urban heat stress. Moreover, we highlight key research topics that will benefit from more integrated use of nature-based solutions and ecosystem services. The framework helps emphasize co-benefits, and can be used to help make co-benefits and multifunctionality explicit in urban decision-making and planning processes.