When the adsorption energy of an organic compound on an Fe(110) surface was evaluated in the presence of 278 water molecules and five acid molecules using the Adsorption Locator module in Materials Studio, the calculated value was unexpectedly large (−3899 kcal·mol⁻¹). In contrast, when the same calculation was performed for the organic molecule in the absence of water and acid, the adsorption energy was much lower (−80.90 kcal·mol⁻¹). This discrepancy raises two important questions: first, what is the underlying reason for such a significant difference between the two cases; and second, what is the correct methodological approach for calculating adsorption energies in complex systems containing solvent molecules? Furthermore, it is necessary to clarify whether the adsorption energy can be taken directly from the values reported in the Materials Studio output tables, or whether a more rigorous reference-state correction is required.