Because voltage-gated ion channels play critical biological roles; understanding how they can discriminate the native metal ion from rival cations in the milieu is of great interest. Although Ca2+, Mg2+, and Na+ are present in comparable concentrations outside the cell, the factors governing the competition among these cations for the selectivity filter of voltage-gated Ca2+ ion channel remain unclear. Using density functional theory combined with continuum dielectric methods, we evaluate the effect of (1) the number, chemical type, and charge of the ligands lining the pore, (2) the pore's rigidity, size, symmetry, and solvent accessibility, and (3) the Ca2+ hydration number outside the selectivity filter on the competition among Ca2+, Mg2+, and Na+ in model selectivity filters. The calculations show how the outcome of this competition depends on the interplay between electronic and solvation effects. Selectivity for monovalent Na+ over divalent Ca2+/Mg2+ is achieved when solvation effects outweigh electrostatic effects; thus filters comprising a few weak charge-donating groups such as Ser/Thr side chains, where electrostatic effects are relatively weak and are easily overcome by solvation effects, are Na+-selective. In contrast, selectivity for divalent Ca2+/Mg2+ over monovalent Na+ is achieved when metal-ligand electrostatic effects outweigh solvation effects. The key differences in selectivity between Mg2+ and Ca2+ lie in the pore size, oligomericity, and solvent accessibility.. The results, which are consistent with available experimental data, reveal how the structure and composition of the ion channel selectivity pore had adapted to the specific physicochemical properties of the native metal ion to enhance the competitiveness of the native metal toward rival cations.