Unmanned aircraft systems are currently being used primarily for military applications, but with the evolution of avionics technology, a huge market in civil applications is emerging. However, most civil applications require unmanned aircraft systems to access non segregated airspace. Current use limitations of non segregated airspace make it extremely difficult to extensively evaluate operational concepts and mission profiles. Using real flights to test the complete unmanned aircraft system mission infrastructure involves costs and risks. Therefore, simulators must be used prior to real flight campaigns to test and validate un manned aircraft system components, and they must take into account all the actors involved in the nonsegregated airspace. This paper describes the development of a software- in-the-loop simulator called ISIS+ to evaluate the automated operations of unmanned aircraft systems in nonsegregated airspace and to test new software components of the unmanned aircraft systems with other avionics components. The ISIS+ simulator provides a realistic simulation environment in which the unmanned aircraft system software components can be developed under real air traffic scenarios while taking into account all the unmanned aircraftsystem’ speculiarities. The unmanned aircraft system is integrated with Early Demonstration and Simulation Platform, an air traffic simulation environment, in order to explore the unmanned aircraft system behavior, conflicting traffic, and air traffic controllers’ requests with the airspace actors. The integration is carried out using automatic dependent surveillance-broadcast messages and considers the unmanned aircraft system as an active actor in the networked environment to simulate future Single European Sky ATM Research and Next Generation Air Transportation System scenarios