The U-space concept was the response of the Warsaw Declaration in 2017 to use drones as a leverage for jobs and new business opportunities. The U-space Blueprint published by the SESAR Joint Undertaking in 2017, states that “U-space is a set of new services and specific procedures designed to support safe, efficient and secure access to airspace for large numbers of drones”. The number of drones' applications is increasing and, with them, the number of drones that will be flying simultaneously in a same geographical area that will need to be safely separated between them and from manned aircraft to allow the maximum number of flights in a given airspace. The separation problem becomes even worst when flights take place in an urban environment where buildings and extreme turbulent wind shear appears close to them. USEPE is aware of these problems and will research on drones’ separation methods in high demanding environments such as cities. This research will be accompanied by a concept of operations that will be implemented and simulated for its validation. USEPE will also research on the use of machine learning algorithms to automate the safe separation and deconfliction of drones while maintaining airspace capacity in different environments and provide the U-space separation management system with artificial intelligence to comply with the statement made in the European ATM Masterplan Roadmap for the safe integration of drones into all classes of airspace. “[…]to take advantage of the latest developments related to technological areas, such as artificial intelligence […]”. In order to obtain valuable results, a casuistic of real urban scenarios will be defined and their feasibility will be assessed to select and implement the more suitable ones and perform a full validation by using the European Operational Concept Validation Methodology (E-OCVM). The research approach will take into account both the strategic and tactical flight phases.