Cyber-Physical Systems (CPS) is a very complex system where a new management layer must be developed. This chapter presents the benefits and challenges of deploying real-time Scheduling, Monitoring, and End-to-End SLA (SMeSLA) in CPS. We propose an SMeSLA conceptual architecture which allows end-users to submit their service level requirements to an SLA manager; as a result, scheduling and monitoring managers would operate accordingly. The SMeSLA management layer empowers CPS system to meet consumers’ satisfaction and achieve optimal performance. However, in order to successfully deploy SMeSLA in CPS, many technical and general challenges must be addressed.