Systems-of-Systems (SoSs) have risen in response to needs of achieving complex missions that can be only carried out from the cooperation among diverse, independent constituent sys- tems. Understanding of missions and emergent behaviors in SoSs as well as the complicated interactions among con- stituent systems are a quite time demanding and challenging tasks. In another perspective, reference architectures (RAs) are a special type of software architecture that promotes reuse of knowledge to develop and evolve software systems, and mainly to promote interoperability among software sys- tems. In spite of the relevance of RAs, these architectures have not still incorporated the concept of missions of SoSs and how to adequately manage them. Hence, such RAs have presented a limited ability to support SoSs development and evolution. In this scenario, the main contribution of this pa- per is to improve the feasibility of RAs in developing SoSs. For this, we present a systematic process to establish, model, and validate missions of SoSs and also incorporate them into RAs. To evaluate our process, we applied it in a RA for SoSs in the healthcare domain. Results achieved until now show that RAs designed considering our process could contribute to decrease expended time and effort at early stages of SoSs engineering.