This book highlights new trends and challenges in research on agents and the new digital and knowledge economy. It includes papers on business process management, agent-based modeling and simulation, and anthropic-oriented computing that were originally presented at the 15th International KES Conference on Agents and Multi-Agent Systems: Technologies and Applications (KES-AMSTA 2021), being held as a Virtual Conference in June 14–16, 2021. The respective papers cover topics such as software agents, multi-agent systems, agent modeling, mobile and cloud computing, big data analysis, business intelligence, artificial intelligence, social systems, computer embedded systems, and nature-inspired manufacturing, all of which contribute to the modern digital economy.