CO2 sequestration in deep geological formations is considered as a promising technology to reduce the impact of CO2 on the greenhouse effect. Practically, large-volume of CO2 could be injected into a system that consists of a highly porous host reservoir covered by a low permeable sealing caprock. High rate injection could result in an abrupt fluid pressures build-up, deforming the aquifer and compromising the integrity of the caprock. The interaction between the high-pressure injected CO2 and the host reservoir as well as the cap rock gives rise to a complex engineering system. A good understanding of this coupled interaction is a crucial issue to secure the underground CO2 injection. This thesis is primarily motivated by such need, and the objectives of the present manuscript are to understand and predict the multiphase flow and thermo-hydro-mechanical processes arising from CO2 injection into deep aquifers and to develop and evaluate both analytical and numerical modelling concepts as reliable prediction and risk assessment tools. For the analysis of CO2 injection-induced deformation of the aquifer, a hydromechanical continuum modelling approach is proposed together with a generalised effective stress concept and an elastoplastic description of mechanical rock behaviour. A deep conceptual aquifer is built, and numerical simulations are run to analyses the effects of hydromechanical couplings and injection strategies on the mechanical stability of the aquifer. The results reveal that upon injection geomechanical instabilities originate from the fluid pressure accumulation within the aquifer, and the most important hydromechanical processes occur in the vicinity of the injection well, compromising the caprock integrity. Low-rate injection significantly reduces the fluid pressure accumulation within the aquifer. However, progressively increasing the injection rate to the target value cannot limit the overpressure development significantly. The temperature of injected CO2 is usually lower than the in-situ temperature, providing additional complexity to the hydromechanical coupling. The hydromechanical framework is extended to include multiphase thermo-hydro-mechanical effects. Numerical simulations are carried out with a finite element reservoir model that is built upon available experimental data and real log data for the CO2 storage site at In Salah, Algeria over an injection period of four and a half years. The blind prediction performed by the fully coupled simulation is in excellent accordance with the real-time monitoring of the surface uplift at In Salah. A coupled analytical approach is also developed to determine the temporal and spatial evolution of caprock deformation and surface uplift when subjected to CO2 injection. Analytical resolution of the plate theory with the abrupt interface theory led to two closed-form analytical solutions that are validated against both in-situ monitoring data at In Salah and finite element modelling results. This development allows to incorporate any fluid injection-induced pressurisation distribution functions in a straightforward way. Thus, advances in hydrogeology research can be integrated easily, and the current development can be extended to any fluid injection and extraction problem. The proposed approach offers a practical solution for determination of caprock and surface deformation, candidate site evaluation and sensitivity analysis of essential parameters.