In the United States, the use and misuse of substances such as tobacco, alcohol, and illicit drugs affect the lives of millions of people as substance use is often an antecedent and a consequence associated with mental and physical illness. Dealing with these challenges requires a greater understanding of substance use in society. In this paper, the authors propose using Model-Based Systems Engineering combined with Addiction Science to represent a framework for improved understanding of substance use as a healthcare structure. Systems modeling language is used to develop a descriptive model of the system architecture, parameters, and interdependencies to illustrate the existing structure of substance use. This paper focuses on the representation and modeling of substance use behavior, which includes the antecedents and consequences of use. The authors have used alcohol use in college students as a case study. The authors propose that the use of systems engineering architecting coupled with Addiction Science will expand the current information base and improve our understanding of substance use. By using a systems engineering approach, the authors not only represent alcohol use in college students but also provide increased information to improve understanding of it thereby creating a framework that can be used to facilitate decision making about substance use.