Nanoporous framework materials are a promising class of materials for energy-efficient technology of xenon/krypton separation by physisorption. Many studies on Xe/Kr separation by adsorption have focused on the determination of structure/property relationships, the description of theoretical limits of performance, and the identification of top-performing materials. Here, we provide a study based on a high-throughput screening of the adsorption of Xe, Kr, and Xe/Kr mixtures in 12,020 experimental MOFs materials, to provide a better comprehension of the thermodynamics behind Xe/Kr separation in nanoporous materials and the microscopic origins of Xe/Kr selectivity at both low and ambient pressure.