Hydrogen production is a topical issue in an energy scenario where decarbonization is a priority, especially with reference to the transport sector that has a great weight on global emissions. Starting from this consideration, GIF (Generation-IV International Forum) investigated the possibility to produce hydrogen by nuclear energy. The “classic” strategy is based on the use of nuclear as energy source for the electrolysis; but on the medium-long term, a more sustainable and smart approach could be founded on the use of thermochemical processes (e.g., I-S) that require a direct coupling of a chemical plant to a nuclear reactor. In order to develop this strategy, it is mandatory to design and optimize all the key components involved in this complex plant. In this study, we developed the 3D-CAD and CFD models of the intermediate heat exchanger (IHX) installed in the Japanese HTTR nuclear power plant. This component is extremely important for both the safety of the two plants and the stability of the whole hydrogen production plant. Initially, our model (developed by AutoCAD 3D and implemented in Star CCM+) was validated on the basis of experimental data available in literature; then, an initial optimization of the IHX testing innovative materials, such as Alloy 617 and ODS−MA754, and a different primary coolant (supercritical CO2) was performed.