In this article, the National Institute on Biodiversity “Alexander von Humboldt” approaches the interaction between science and policy based on three case studies in which the Institute is advancing in mainstreaming biodiversity and ecosystem services into urban-regional planning. This project is coordinated by the Policy Program and actively supported by the Information and Knowledge Management and the Communication and Social Awareness programs of the Institute. The structure of this project is motivated by “integrative science” principles and is framed by the following institutional missions: (i) To strengthen scientific knowledge on BD and ESS based on robust and rigorous analysis and tools; (ii) To make this information valuable, indispensable and “readable” to policy-makers’ inquiries; and (iii) To spread scientific knowledge socially in order to promote citizens’ awareness and responsibility. Some of the questions to be solved or reconsidered during this research are: What information is needed to mainstream biodiversity and ecosystem services into urban-regional planning? How do we generate useful knowledge to society in order to reach real sustainability of and within cities? How do we integrate this knowledge into policy decisions? How do we make this information valuable to citizens? Policy agents are to be supported by technical inputs to analyze and model how BD and ESS respond to changes with uncertain degrees of intensity and consequences and how this affects human wellbeing and ecosystems’ sustainability. Taking into account these future scenarios, decision makers will be able to define and adopt policies and also promote social behaviors towards adaptability and resilience; therefore achieving real sustainable conditions. Policy makers need to understand that one of the most challenging issues to be resolved is to mainstream BD and ESS conservation outlines into urban policies and therefore advance in achieving real sustainability.