This Special Issue of Energies, “Smart Cities and Positive Energy Districts: Urban Perspectives in 2021”, introduces contemporary research on Smart Cities and on Positive Energy Districts. The present Special Issue, namely the fourth Special Issue, Smart Cities and Positive Energy Districts: Urban Perspectives in 2021, has been dedicated to tools, technologies, and system integration for Smart Cities and for Positive Energy Districts. The topic highlights the variety of research within this field, including research on: tools facilitating the evaluation of Sustainable Plus Energy neighborhoods, of enabling-technologies and procedures for Positive Energy Districts, and of multicriteria assessment for the identification of Positive Energy Districts; system integration related to optimized energy and air quality management in the COVID-19 scenario; system integration upgrading existing residential areas to the status of Positive Energy Districts; and renovation models for large scale actions.