The hyperspectral (HSR) sensors Earth Surface Mineral Dust Source Investigation (EMIT) of the National Aeronautics and Space Administration (NASA) and Environmental Mapping and Analysis Program (EnMAP) of the German Aerospace Center (DLR) were recently launched. These state-of-the-art sensors have joined the already operational HSR sensors DESIS (DLR), PRISMA (Italian Space Agency), and HISUI (developed by the Japanese Ministry of Economy, Trade, and Industry METI and Japan Aerospace Exploration Agency JAXA). The launching of more HSR sensors is being planned for the near future (e.g., SBG of NASA, and CHIME of the European Space Agency), and the challenge of monitoring and maintaining their calibration accuracy is becoming more relevant. We proposed two test sites: Amiaz Plain (AP) and Makhtesh Ramon (MR) for spectral, radiometric, and geometric calibration/validation (CAL/VAL). The sites are situated in the arid environment of southern Israel and are in the same overpass coverage. Both test sites have already demonstrated favorable results in assessing an HSR sensor’s performance and were chosen to participate in the EMIT and EnMAP validation stage. We first evaluated the feasibility of using AP and MR as CAL/VAL test sites with extensive datasets and sensors, such as the multispectral sensor Landsat (Landsat5 TM and Landsat8 OLI), the airborne HSR sensor AisaFENIX 1K, and the spaceborne HSR sensors DESIS and PRISMA. Field measurements were taken over time. The suggested methodology integrates reflectance and radiometric CAL/VAL test sites into one operational protocol. The method can highlight degradation in the spectral domain early on, help maintain quantitative applications, adjust the sensor’s radiometric calibration during its mission lifetime, and minimize uncertainties of calibration parameters. A PRISMA sensor case study demonstrates the complete operational protocol, i.e., performance evaluation, quality assessment, and cross-calibration between HSR sensors. These CAL/VAL sites are ready to serve as operational sites for other HSR sensors.