The chemo-hydro-mechanical (CHM) interaction between swelling Eurobitum radioactive bituminized waste (BW) and Boom Clay is investigated to assess the feasibility of geological disposal for the long-term management of this waste. These compatibility studies include laboratory water uptake tests at the SCK-CEN, and the development of a coupled CHM formulation for Eurobitum by the International Center for Numerical Methods and Engineering (CIMNE, Polytechnical University of Cataluña, Spain). Two nearly constant volume water uptake tests were stopped after 1036 and 1555 days to characterize the morphology of the hydrated BW samples and to visualize the hydrated part with microfocus X-ray Computer Tomography (µCT) and Environmental Scanning Electron Microscopy (ESEM). After about four years of hydration in nearly constant volume water uptake tests, pressures up to 20 MPa are measured. During this hydration period only the outer layers with a thickness of 1–2 mm were hydrated, and only about 10–20% of the initial NaNO3 content was released by the samples. The experimental results of pressure increase and NaNO3 leaching, as well as observations on µCT and ESEM images, were reproduced rather successfully by the coupled CHM formulation for Eurobitum BW.