Future human expeditionary missions such as return to the Moon or initial Martian expeditions must deal with new mission modes, mission environmental diversity, and extended mission durations. Two recently emerging technology capabilities, Virtual Environment (VE)/Virtual Reality (VR) and Computer Aided Design (CAD)/Computer Aided Engineering (CAE)/Computer Aided Manufacturing (CAM) enhanced capability, when used in combination with a systems engineering focus on systems effectiveness and availability, can make the difference in supporting human expeditionary systems design, development, manufacturing, and operations (flight and surface).Mission durations for human permanent lunar operations and initial and follow-on Martian expeditions will require a significant focus on system effectiveness. The systems effectiveness availability component has subsets of reliability, maintainability, operability, spares number and location, transportation capability, and “others”. The recent advent of the CAD technology which permits the “form and fit” check-out and verification via a computer based design system permits new avenues to be explored in systems engineering to assure system effectiveness in the final operational design and subsequent operations.The same CAD/CAE/CAM engineering data bases that are used above can then be used as a foundation for virtual reality or virtual environment capability to provide additional verification of the practicality of the design. The Life-of-the-Program (LOTP) use of this virtual environment technology can be used by the flight crews for general and recurrent training for pre-mission activities and for in-mission operational support.Human expeditionary missions contain a rich complement of system engineering design challenges. Outpost and permanent lunar operations will place high demands on systems availability and minimum logistic systems. Mars human expeditionary missions require sustainable operations, often in an autonomous or robotic mode, with little or no logistics available to those assets that have been forward deployed under a split mission scenario.For the purposes of discussing both lunar and Mars human expeditionary missions the utilization of the “split” mission concept will be utilized. The “split” mission concept employs the use of a cargo mission first as the forward deployment of assets for the mission and incorporates the use of autonomous or robotic emplacement and initial readiness of all the systems before commitment to a crew launch. The subsequent launch in the “split” mission concept is the crew launch. In the case of lunar mission, that could be a month after the cargo mission. In the case of a Mars mission, that duration would be 26 months later due to the recurring orbital dynamics of the Earth-Mars system.The advent of capabilities to conduct system engineering with the use of CAD/CAE/CAM capabilities and VE/VR technologies permits the mission and systems developers to meet the above challenges with a degree of assurance not achieved in prior space systems applications.This paper will discuss the diverse nature of the lunar and Mars environment, the lunar and Mars operations related to human expeditionary mission, the systems engineering implications including the decomposition of basic mission timelines, the fusion of CAD/CAE/CAM and Virtual Environment (Virtual Reality) technologies, and the Life-of-the-Program utilization of those fusion capabilities.