Epoxy−amine systems are ubiquitous in the field of industrial thermosetting polymers, often used in a moist atmosphere. In addition, previous studies showed amine−metal interactions through the formation of an interphase, with the formation of surface complexes that may involve the formation of water molecules. However, to date, the impact of water on an epoxy/amine−metal interphase has not been specifically addressed. In this work, we examined for the first time the role of this potential fourth component by way of a dual experimental/computational approach. The effect of water on the glass-transition temperature of the obtained polymers was quantified. The in situ formation of a DETA−Al−water interphase was followed by mixing calorimetry. The DETA−water interaction was highly exothermic, and the underlying mechanism was discussed on the basis of DETA hydration, which was confirmed by density functional theory (DFT) and Monte Carlo simulations. Taking into account the pre-existing interaction between diethylenetriamine (DETA) molecules allowed us to model all experimental data. Comparison of experimental and calculated IR spectra contributed to validate the simulation parameters used. Our findings indicate that the presence of water may noticeably affect epoxy−amine-based systems. Mixing calorimetry and computational modeling appear as particularly adapted tools for the comprehension of such complex systems.