The paper examines the interaction between host rock and a clay-based engineered barrier in the context of deep underground disposal of high-level radioactive waste. A large scale “in situ” heating test currently under way in the underground Grimsel Rock Laboratory (GRL; Switzerland) is adopted as a representative case for study. The main features of the behaviour of the rock/barrier system have been examined using a comprehensive programme of coupled thermo–hydro–mechanical analyses. A parametric study has been performed to assess the effects of individual phenomena and parameters. The characterisation activities carried out in relation with the in situ test provide the information on material properties and test conditions required. Results highlighting the influence of vapour diffusion, permeability, and retention curve of rock and bentonite are presented. The interaction between clay barrier and host medium exhibits a high degree of complexity.