Shale and clay-rich rock formations have been considered as potential host rocks for geological disposal of high-level radioactive waste throughout the world. Coupled thermal, hydrological, mechanical, and chemical (THMC) processes have a significant impact on the long-term safety of a repository in this type of rocks. The validity of the two-part Hooke’s model (TPHM), a new constitutive relationship, and associated formulations regarding rock hydraulic/mechanical properties is demonstrated by the consistency between observations from a mine-by test at the Mont Terri site in Switzerland and the predictions from a three-dimensional model for the test. A three-dimensional computational method capable of addressing fracture initiation and propagation as a THM coupled process has been further developed and tested. The R&D group also developed a three-dimensional model for the Full-Scale Emplacement Experiment (FE) tests at the Mont Terri site in Switzerland that gives satisfactory temperature evolution near the heater. They also conducted for the first time a THM analysis involving the Barcelona Basic Model (BBM) in a full three-dimensional field setting for modeling the geo-mechanical behavior of the buffer. The analysis highlights the complex coupled geo-mechanical behavior in the buffer and its interaction with the surrounding rock.