Ligand-exchange chiral extraction (LEXCEX) is an emerging technology for large-scale continuous resolution of enantiomers of amino acids and a wide range of chiral therapeutics and drug precursors. LEXCEX is based on the ability of a chiral ligand (Li), solubilized in the non-aqueous phase of a water/alcohol two-phase system through complexation with a transition metal ion (i.e., Cu), to preferentially extract one enantiomer (En) into the organic phase through formation of a ternary Li: Cu: En electroneutral complex. Here we show that the efficiency of the extraction depends, often strongly, on a number of process variables, including the selectivity of the ligand, the solubility of the enantiomers and complexes containing them in the organic phase, pH and transition-metal ion (Cu) concentration. Phase-equilibria in LEXCEX systems is governed by the complex chemical equilibria in both the aqueous and organic phases, To better understand this extraction process, we develop a model for ligand-exchange chiral extraction which couples a complete description of chemical equilibria in each phase with the overall phase equilibria of the system. The model requires the complete set of protonation constants and binary and ternary formation constants for each species present in either the aqueous or organic phase. When coupled with phase equilibrium constraints, the model quantitatively predicts extraction performance as a function of key operating parameters, thereby providing a simple computational approach to process optimization. Measured equilibrium formation constants for ternary complexes containing the N-decyl-L-hydropxy-proline ligand are found to depend strongly on solvent environment, with complex stabilities in general decreasing when the complex is transferred from water to n-octanol. The role of solvent in ternary complex stability is explored through a series of molecular mechanics simulations.