The 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 16th International KES Conference on Agents and Multi-Agent Systems: Technologies and Applications (KES-AMSTA 2022), held at Rhodes, Greece in June 20–22, 2022. 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.