This work summarizes the radiation transport–based design for a new D2O-moderated ex-core irradiation facility in the Washington State University (WSU) TRIGA reactor for optimization of 135Xe sources used for calibration and quality control testing of Xe gas detection equipment in support of the Comprehensive Test Ban Treaty (CTBT). Three-dimensional (3-D) particle transport analysis characterizing the WSU reactor core using MCNP6.2 (3-D Monte Carlo) and PENTRAN (3-D deterministic parallel SN) form the basis for the computational optimization. Excellent agreement between MCNP6.2 and PENTRAN predictions is observed. A fundamental fuel bundle depletion analysis is applied to enable a more accurate prediction of neutron flux and neutron spectrum distribution, which drives production rates of 135Xe and 133Xe. The results of various model simulations were used to inform recommendations for the final irradiation chamber design, which has been optimized for safe placement in the reactor tank prior to startup and will allow for insertion and rotation of xenon “bean” samples using existing WSU irradiation equipment, while remaining within operational parameters. The irradiation chamber is expected to produce samples that will remain viable for use in CTBT standards applications for durations 70% to 80% longer than samples produced using current procedures. Thus, this design is expected to improve CTBT-related calibrations and performance testing and to support the continued stability of the CTBT monitoring network.