The regeneration of urban streetscapes through Nature-based Solutions is crucial for achieving climate neutrality and resilience. However, design research is limited to date and needs to impact current design and planning practices. Ongoing research attempts to go beyond present gaps to define an operational methodology and guidelines to mainstream streetscape’s climate-resilient nature-based regeneration. The research adopts a Research-by-Design approach, structured in three integrative phases: (i) Research of Design, (ii) Research through Design, (iii) Research for Design. The contribution will go through the first two phases by applying and cross-testing the operational methodology in two neighbourhoods in Matera, Italy and Riyadh, Saudi Arabia.