Finding new solutions and strategies to enhance the sustainable management of urban systems is among the most important challenges of this era. Currently, cities consume about 70% of the global energy and it is expected that in 2030 about 60% of the global population will live in cities that account for only about 2% of the Earth surface. At European level, there is a higher concentration of population in medium and small cities compared to mega-cities, with about 80% of the European population living in cities with less than 250,000 inhabitants. This is mainly due to the gradual expansion of the ancient (mostly medieval) settlements over time. European Commission provided an important contribution for the sustainable development of urban systems through the Green Public Procurement (GPP) policy. Nonetheless, the implementation of eco-innovation processes in European countries is still slow. This study proposes a multi-criteria framework to assess the sustainability of cities at different scales. The framework is based on several topics of interest for AScUS, among which “Sustainable cities”, “Circular economy at the Urban-Scale”, and “Policy and Governance toward Urban Sustainability”. In particular, the framework integrates environmental and socio-economic indicators for a comprehensive assessment of urban systems. First applications of the framework will target small and medium cities. The framework can be used in support of the drafting of guidelines and procedures through which local authorities, in line with the GPP policy, can contribute to the achievement of sustainability targets for urban systems.