NASA has outlined a phased approach to expand human presence deeper into the solar system starting with the Moon. Phase 1 of this plan begins in the 2020s with missions in cislunar space and assembly of the Gateway. The Gateway is an evolvable, flexible, and modular space platform in lunar orbit. It can support initial crewed missions of 30 days, with the potential to increase mission duration for later missions. When the Gateway is uncrewed, robotic science missions will be performed. The Gateway allows astronauts to practice the skills and test technologies needed for months and years beyond low Earth orbit. A key to success for these deep space missions will be carefully coordinated operations by ground support, flight crew, and autonomous spacecraft. Lockheed Martin Space is designing Gateway concepts as part of NASA’s NextSTEP study contract. Additional operational considerations will be made to accommodate science payloads that would use the Gateway as a communication relay, platform for in-space or remote robotic missions to the lunar surface, and remote experiments during untended periods. The Gateway is modular in design to incorporate international cargo and logistics modules, additional habitat modules, and perhaps crewed lunar landers. These operational considerations are also being designed into the system. Working through the operational practices and relationships between the crew and ground control at the Gateway will provide the groundwork for future missions to Mars requiring more autonomy, such as Mars Base Camp missions. For example, robotic operations on the lunar surface, conducted by scientist astronauts, are directly translated to the exploration of the Martian surface by rovers and unmanned aerial vehicles from a Mars orbital platform. As preparations are made for missions to Mars, more autonomy will be required and the interactions between the crew, ground, and autonomous spacecraft systems need to be refined.