This opinion paper describes the major coupled T(Thermal)-H(Hydro)-M(Mechanical)-C(Chemical) processes in geological repository systems and the frontier of related model development. Particular focus is made on the analysis of existing approaches and open research questions with respect to the further development of coupled codes and models for realistic multi-scale simulations of repository systems. These include the use of machine learning and artificial intelligence in acceleration of computer codes; sensitivity analysis, inverse modelling and optimisation; software engineering and collaborative platforms for model development.