Systems integration is a major challenge across many disciplines, with a large number of technical, project, organisational or environmental problems occurring as a result of improper integration. This article highlights the scope of the challenges facing systems integration and explains why it requires the incorporation of both technical and non-technical domains. Humans, systems and the environment, as well as the interactions among them, significantly contribute to the proper integration of systems. These, however, have been formulated differently across different engineering disciplines. For example, systems engineering considers the human to be part of the system, while railway engineering considers the human to be part of the system environment. This paper explores the fundamentals of integration and lays a theoretical foundation for the integration of systems. It will introduce Safety Cube theory to outline these fundamental aspects of system integration. Example applications are provided at the end of the paper.