System-of-systems (SoS) thinking and optimization can applied in the setting of healthcare, specifically radiation oncology. The SoS example investigated was the radiation treatment planning process. A hypothetical set of software and staffing positions were considered as systems that each had a specific set of characteristics, capabilities, and interfaces that impact the overall operation of the SoS. This was a proof of concept study. To improve patient care and limit waste within this process, a Fuzzy Inference System (FIS) was developed based off the key performance attributes (KPAs) of accuracy, safety, affordability, timeliness, and robustness. The equation defined KPAs were used to calculate the overall fitness value in a genetic algorithm to find the optimized meta-architecture. Using a SoS fuzzy inference optimization approach can potentially limit waste and improve overall healthcare operations.