The explosive growth of the city of São Paulo starting in the 1940s resulted in vast expansion with little attention to the characteristics of the natural landscape. This resulted in extreme modification of the water system, including canalization, piping and covering of streams. Due to these modifications and the related urban structure, São Paulo’s faces multiple difficulties regarding climate change adaptation. Therefore, this thesis aims to develop an urban regeneration strategy based around the lost natural systems in order to counter the effects of climate change and simultaneously improve the living environment within the city. From literature it appears that green-blue infrastructure can potentially be a strong tool in adapting a city to the effects of climate change, while providing multiple other benefits. As within the city the water system is closely related to the infrastructural system and because there is constant threat of informal settlements next to valuable landscape areas including the streams, there are several difficulties in developing a strategy based around the natural system. The strategy provides an holistic approach in which a multi-functional ecological axis is developed alongside the natural course of a stream as backbone of a green-blue network. Together with the implementation of infrastructural axes and several smaller interventions within the public realm, the strategy provides an answer to the problems São Paulo is facing.