Climate shocks such as extreme floods and storms, droughts and heatwaves have complex, inter-connected and far-reaching consequences across multiple policy sectors and systems. Shocks in other systems, such as financial or health crises, can, in turn, affect climate challenges. Applying a systems approach to climate change helps policymakers understand linkages between issues that are treated separately and propose cross-sectoral, multi-disciplinary solutions in cities. This paper proposes a four-pronged policy framework to disentangle the different elements of economic, social, environmental, and other systems operating in cities, maximise co-benefits and manage trade-offs across systems, and build systemic climate resilience in cities. It summarises the contribution of the Working Party on Urban Policy and the Regional Development Policy Committee to the 2021-2022 OECD Horizontal Project on “Building Climate and Economic Resilience in the Transition to a Low-Carbon Economy”.