The effect of alkali and transition metal cations in the formation of host-guest complexes with the water-soluble p-sulfonatocalix[4]arene (SC4) was studied using 2-chloropyridine and Na+ and Cu2+ as model guest and model cations, respectively. The results obtained from isothermal titration calorimetry and NMR experiments provide evidence for the formation of 1:1:1 ternary complexes for both cations with Cu2+ showing positive cooperativity and Na+ negative cooperativity. The formation of ternary complexes comprising transition metal cations has been scarcely explored but present high potential for devising catalytic systems/models or for enhancing the stability and selectivity of SC4 complexes. Because transition metal cations are usually present in solution together with other SC4 countercations (e.g., Na+), a general binding model that considers the dynamic formation of all possible complexes (including ionic exchange between ternary complexes) is presented. This model allows the optimization of the conditions required to selectively form target complexes.