Thermodynamic hydrate inhibitors (THIs) are chemical compounds that are utilized to reduce the activity of water and consequently restrict the hydrate formation zone, which is managed as a result of strong molecular/ionic interactions with water without further participating in the hydrate structure. In this regard, developing a precise and easy-to-use thermodynamic relation to calculate the activity of water in the presence of aqueous THI such as alcohols and salts is of great importance. Such a relation can then be employed within a thermodynamic approach to model hydrate equilibria. The goal of this work was to derive a relationship from the Gibbs−Duhem theory to calculate hydrate dissociation temperatures in the presence of aqueous alcohol + salt solutions. As such, the interactions between salts and mixed solvents (water + alcohol) were described phenomenologically using the Bromley model. The results find applications in the gas and oil industry. To describe the hydrate phase, the van der Waals−Platteeuw (vdW-P) model was utilized. The Peng−Robinson equation of state (EoS) was used to describe the gas phase. To calculate the activity of water in the salt-free water + alcohol solution, the UNIQUAC and Flory models were employed, and to calculate the activity of water in the alcohol-free water + salt solution, the Bromley and Pitzer models were employed. The predictions of the model were compared to the Delavar and Haghtalab, Mohammadi and Tohidi, and Hu-Lee-Sum (HLS) calculations. The new approach developed herein yielded accurate results for a databank of 613 data points of gas hydrate dissociations in the presence of alcohol solutions with average absolute deviations (AAD) of 0.79 K. For prediction of the gas hydrate dissociation temperature in the presence of aqueous salt solutions, the vdW-P + PR + Bromley model resulted in a notably enhanced accuracy with an AAD of 0.52 K for 1065 data points. Our research concludes with the superiority of this work, when the activity of water was used together with vdW-P + PR + UNIQUAC + Bromley. With an AAD of 0.68 K for 544 data points, the model reliably predicted gas hydrate dissociation temperatures in the presence of aqueous alcohol + salt solutions.