The partitioning of a substrate from one phase into another is a complex process with widespread applications: from chemical technology to the pharmaceutical industry. One particularly well-known and well-studied example is 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane) trafficking through the lipid bilayer. Halothane is a model volatile anesthetic known to impact functions of model lipid bilayers, altering the structure and thickness upon its partitioning from the bulk phase. A number of theoretical and experimental investigations suggest the importance of electronic polarizability, determining a preference for halothane to partition in the interfacial systems as in lipid bilayers or binary solvents. The recently published protocol for the development of polarizable force fields based on the classical Drude model has provided fresh impetus to efforts directed at understanding the molecular principles governing complex thermodynamics of the hydrophobic hydration. Here, molecular simulations were combined with free energy simulations to study solvation of halothane in polarizable water and methanol. The absolute free energy of halothane solvation in different solvents (water, methanol, and n-hexane) has been evaluated for additive and polarizable models. It was found that both additive and polarizable models provide an adequate description of the halothane solvation in high-dielectric (polar) solvents such as water, but explicit accounting for electronic polarization is imperative for a correct description of the solvation thermodynamics in nonpolar systems. To study halothane dynamics in binary mixtures, all-atom molecular dynamics (MD) simulations for halothane-methanol mixtures in a wide range of concentrations were performed alongside an analysis of structural organization, dynamics, and thermodynamic properties to dissect the molecular determinants of the halothane solvation in polar and amphiphilic liquids such as methanol. Additionally, a theoretical test of the hypothesis on the weak hydrogen bonding of halothane and methanol in the condensed phase is provided, which was presented on the basis of spectroscopic analysis of the C-H vibrations in different gas-phase complexes. The simulations performed in the condensed phase suggest that hydrophobic interactions between halothane and methanol play a dominant role in preferential solvation.