This study presents a thermodynamic framework for predicting synergistic mineral dissolution and buffering in wastewater treatment systems. Buffering is essential for stabilizing wastewater composition against pH fluctuations and ionic disturbances caused by variable chemical inputs. The model addresses multicomponent heterogeneous systems containing both soluble and insoluble species, focusing on key minerals such as struvite and vivianite that play a central role in nutrient recovery and contaminant immobilization. A key innovation of this framework is its ability to describe coupled mineral dissolution and precipitation processes through a unified set of thermodynamic equations. These incorporate mass balance constraints and equilibrium expressions involving metal ion hydrolysis, metal ion–ligand complex formation, and protonation reactions. The influence of competing ions, such as magnesium, calcium, sodium, and carbonate, is also considered, as they directly affect system buffering and mineral phase stability. Another major contribution is the introduction of the synergistic coefficient, a novel parameter that quantifies the enhancement of buffering and dissolution beyond additive behavior. This allows comparative assessment of synergistic potential across different wastewater compositions. It is demonstrated that two conditions are required for the manifestation of synergistic effects in wastewater systems: (a) the formation of a ternary complex, and (b) amplification of one or more physicochemical properties. Struvite satisfies both criteria, as it forms a stable solid ternary complex and exhibits enhanced solubility and buffering action under appropriate conditions. Thermodynamic analysis reveals that these synergistic effects arise from the formation of mixed-ligand complexes that stabilize pH and promote mineral recovery. Validation using real wastewater confirms the model predictive accuracy in identifying optimal pH and ion ratios. The thermodynamic relations derived from this study enable the design of new synergistic processes with targeted buffering and mineral recovery properties, supporting the advancement of sustainable and efficient wastewater treatment technologies.