The two-volume set LNBIP 535 + 536 constitutes selected papers from the 21st European, Mediterranean, and Middle Eastern Conference, EMCIS 2024, which was held in Athens, Greece, during September 2-3, 2024. EMCIS covers technical, organizational, business, and social issues in the application of information technology and is dedicated to the definition and establishment of Information Systems (IS) as a discipline of high impact for IS professionals and practitioners. It focuses on approaches that facilitate the identification of innovative research of significant relevance to the IS discipline following sound research methodologies that lead to results of measurable impact. The 53 papers presented in the proceedings were carefully reviewed and selected from a total of 152 submissions. They were organized in topical sections as follows: Part I: Artificial Intelligence; Blockchain Technology and Applications; Metaverse, Immersive Technologies and Games; Smart Cities; Classical and Emerging Digital Governance – The Artificial Intelligence Era; Part II: Management Information Systems; Advanced Topics in Information Systems; Core Topics in Information Systems; Information Systems Security, Information Privacy Protection and Trust Management.