Interoperability in the Energy System is an important topic for the development of Smart Grids. In this paper we introduce a structured approach to solve the complex interoperability issues of connected systems and sub-systems based on experiences from the healthcare enterprise, where formerly rather closed systems were successfully migrated towards more open system. This approach combines well-established use case methodologies from the software development domain with benefits of the concept of integration profiles which can be found in the healthcare domain. The combination of the two methods is demonstrated by developing an integration profile for an application example from the Smart Grid domain; the virtual power plant operation use case. Using the presented method, a step-by-step guideline for implementers could be created. The profiling methodology seems to be an appropriate method to approach complex interoperability issues of Energy Systems and may be expanded to other fields.