An original thermodynamic framework has been developed to describe precipitation–dissolution phenomena of drugs in aqueous systems containing cyclodextrins and auxiliary agents. The central innovation is the degree of drug precipitation, derived from new mass balance equations combined with the Law of Mass Action. This parameter quantifies the fraction of drug present in the solid phase and directly indicates solubility limitations under defined conditions. The methodology allows determination of species distributions—including free drug, ionized forms, binary complexes, and ternary complexes—across aqueous and solid phases as functions of pH and composition. Species molar fractions are normalized to the total apparent solubility, ensuring internal consistency. To support visualization, Diagrams of Heterogeneous Chemical Equilibria were introduced, involving three steps: (i) thermodynamic evaluation of solid-phase stability using precipitation degree, (ii) calculation of molar fractions within stability regions, and (iii) assessment of homogeneous systems containing only soluble species by conventional equilibrium methods. Application to ten commercial drugs, including cimetidine, flurbiprofen, indomethacin, and naproxen, confirmed the predictive capacity of the model. By integrating available equilibrium constants, the methodology quantitatively predicts the extent of drug precipitation and reveals synergistic effects in drug–cyclodextrin–auxiliary agent systems. These predictive advantages are particularly relevant for poorly soluble pharmaceuticals, as the framework identifies conditions where solubility is maximized and precipitation minimized. Overall, the proposed methodology provides both quantitative and graphical tools for analyzing phase behavior, solubility dynamics, and cooperative effects in drug formulations. Beyond pharmaceuticals, the framework has potential applications in environmental and materials science where heterogeneous equilibrium processes of poorly soluble compounds are critical.