This Handbook explores new and old theoretical, methodological, and empirical insights and perspectives on entropy, complexity, and spatial dynamics. A central and cross-cutting theme of the Handbook is the role of entropy in complex, dynamic spatial socio-economic systems as both a measure of spatial complexity and a process involved in the dynamics and emergent behavior of spatial systems. In this regard, one of the bold aims of the Handbook is to examine how and to what extent entropy is (or might be) a universal principle dictating and describing the structure and dynamics of complex spatial systems across different domains and applications. To this end, the Handbook draws upon perspectives from various disciplines _ from economics to geography to physics to biology to information science. Starting from these considerations, this introductory chapter summarizes classic and state-of-the-art cross-disciplinary methods and approaches for modeling and characterizing complex, dynamic, integrated networked spatial systems, including entropy-based and information-theoretic frameworks and derivations, considering relevant theoretical underpinnings. First, this introduction presents a concise history of the foundational concepts, theories, and models behind spatial economic science, from entropy to complexity to spatial dynamics. It then provides a high-level and more detailed overview of the Handbook. Finally, the chapter reflects on the extent to which the emerging insights originate from conventional, old developments and how new models and methods can help inform policymaking and planning, particularly for addressing contemporary issues and challenges tied to our increasingly integrated, uncertain, and dynamic world.