The report focuses on the contribution that STI practices make towards mitigating some of the most pressing sustainability challenges facing the urban socio-technical systems in a post-COVID-19 world. The report also assesses the urbanization trends and the impact of the pandemic on sustainable urban development. It identifies 12 key urban sustainability challenges: energy, circularity, water, mobility, economic prosperity and financial stability, housing, education, gender empowerment & equality, urban planning, healthcare, safety and security, and protection from natural disasters. For each category, a selection of practical STI solutions and innovative case studies worldwide are presented. Finally, the report calls for action at the national and international level to seize the innovation momentum from the COVID-19 pandemic and to use the transformative power of STI to deliver on the commitment to sustainable urban development. Governments should prioritize the STI solutions that ensure value for money and more efficient spending, focusing on activities that boost urban resilience. International cooperation efforts will be needed to further pool, formalize and transfer the available knowledge on effective STI solutions.