A thermodynamic-based procedure was developed that is capable of predicting the incipient hydrate dissociation temperature in the presence of a single electrolyte or organic inhibitor aqueous solution. In the proposed framework, the two-suffix Margules activity model is used to take into account the concentration of inhibitor and the Clausius–Clapeyron approach is employed to calculate the hydrate dissociation enthalpy. The presented model uses the Peng–Robinson (PR) equation of state (EoS) to compute the compressibility factor of the gas phase. The introduced model is then specified for predicting the methane-hydrate dissociation temperature (MHDT) in the presence aqueous solutions of NaCl, KCl, CaCl2, MgCl2, methanol, ethylene glycol, diethylene glycol, triethylene glycol, 1-propanol, and 2-propanol. Finally, the optimal values of the Margules coefficient are obtained due to the type of additive. The proposed model for MHDT estimation provides consistently satisfactory results. Absolute deviations between the model predictions and corresponding experimental data for all studied systems are less than 1 K across the investigated pressure and temperature ranges.