This study examines an approach to model and analyze the transforming health-information system of systems. The process and architecture for the Cambodian malaria-surveillance system were modeled using the Engineering Systems Multiple-Domain Matrix modeling framework. By using the attributes of the process, architecture, and risk associated with the environment within the model, relative weights of the constituent systems were scored at each interval of time. The simulated confidence intervals of the absolute difference in the scores indicated that this approach captured the transformation of the system under investigation. This approach provides the first step in analyzing the transitional conditions of constituent systems as well as the entire health-information system, whereby informed decision-making for optimizing continuous system management is facilitated.