Challenges emanating from rapid urbanisation require innovative strategies to transform cities into global climate action and adaptation centres. We provide an analysis of the impacts of rapid urbanisation in the Gauteng City-Region, South Africa, highlighting major challenges related to (i) land use management, (ii) service delivery (water, energy, food, and waste and sanitation), and (iii) social cohesion. Geospatial techniques were used to assess spatio-temporal changes in the urban landscapes, including variations in land surface temperatures. Massive impervious surfaces, rising temperatures, flooding and heatwaves are exacerbating the challenges associated with rapid urbanisation. An outline of the response pathways towards sustainable and resilient cities is given as a lens to formulate informed and coherent adaptation urban planning strategies. The assessment facilitated developing a contextualised conceptual framework, focusing on demographic, climatic, and environmental changes, and the risks associated with rapid urbanisation. If not well managed in an integrated manner, rapid urbanisation poses a huge environmental and human health risk and could retard progress towards sustainable cities by 2030. Nexus planning provides the lens and basis to achieve urban resilience, by integrating complex, but interlinked sectors, by considering both ecological and built infrastructures, in a balanced manner, as key to resilience and adaptation strategies.