Consumers' prescription drug decisions are affected by a number of structural, psychological, and health communication source variables. To provide a theoretically sound and comprehensive prescription medication decision engagement framework, this study integrated Andersen's Health Service Use Model to address contextual and structural factors, the Health Belief Model (HBM) to examine psychological factors, and extant research on the influence of various health communication sources to explain the prescription drug decision engagement mechanisms of health information-seeking intention, prescription drug-seeking intent, and prescription-seeking behavior. Employing survey methodology, the framework was tested using a sample of U.S. adult consumers (N = 370). Results demonstrated the utility of the integrated model for explaining consumers' participation in their prescription decisions. Specifically, consumers' assessment of target health behaviors and the use of various health communication sources significantly improved the explanatory power of the decision engagement model beyond structural factors. The results impart valuable theoretical contributions and have the potential to guide public health interventions related to consumers' prescription drug decisions.