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Humanity is standing on the cusp of its next giant leap – an international, sustainable, and commercial return to the moon. Unlike the Apollo missions, the expectation that a permanent human presence will be established is well founded. Initially, crewed missions to the lunar surface are expected to last between 6 and 30 days and occur approximately once per year, however the robust suite of landers and orbiting assets proposed by both commercial and government entities provide an opportunity to conduct science research on the moon and in cis-lunar space, 24x7 for many years. In the 50 years since the conclusion of Apollo, NASA’s crewed space science missions have been evolving. This can be seen clearly from Skylab and the Space Shuttle’s Spacelab to the International Space Station (ISS). Presently aboard the ISS, international crews spend nearly half their time working on experiments while many payloads collect science non-stop with either very limited, or no crew interaction. Additionally, a fleet of orbiting experiments complement and validate those investigations performed on the ISS. As the number, variety, and complexity of these investigation increase, it becomes ever more necessary to integrate across the many entities involved to prevent duplication of effort, ensure complementary results, reduce cost, and create a sustainable environment to conduct groundbreaking scientific research in space. In this paper, we examine how the various elements of the Artemis program including NASA’s Lunar Gateway, Commercial Lunar Payload Services (CLPS) endeavor, the Human Landing Systems (HLS), surface habitats, rovers and many more will be operated to ensure interoperability, maximize science return, and enable success for government, commercial and private partners.