Abstract: Accurate prediction of deoxidation equilibria in Fe-based melts is essential for oxygen control and inclusion engineering, but remains difficult because conventional thermodynamic models are limited in describing both finite-concentration effects and strong short-range ordering in liquid alloys. In this work, a structure-informed coupled method (SICM) is developed by combining the unified interaction parameter formalism (UIPF) with the modified quasi-chemical model (MQM). In the proposed framework, weak interactions in the solvent-rich matrix are described by the UIPF, whereas strong solute-oxygen associations are represented by the MQM. Composition-dependent coordination numbers and binary mixing enthalpies are further introduced to define the atomic pairing sequence and coupling weights. The model is validated for the Fe–Al–O and Fe–Si–O systems using 193 experimental datasets at 1873 K and is further extended to the Fe–Cr–Al–O system. Compared with the evaluated thermodynamic models, the SICM gives the lowest prediction errors for the Fe–Al–O and Fe–Si–O systems and maintains comparable accuracy for the Fe–Cr–Al–O system, with mean absolute percentage errors of 10.0%, 6.2%, and 20.5%, respectively. The results indicate that incorporating structural information into a coupled thermodynamic framework improves the description of deoxidation behavior over a wide composition range.