The effectiveness of the interactions between various alkyl ammonium cations and the well-defined spherical Keplerate-type {Mo₁₃₂} capsule has been tracked by ¹H DOSY NMR methodology which reveals a strong dependence of the self-diffusion coefficient of the cationic guests balancing from the solvated to the plugging situations. Analysis of the data is fully consistent with a two-site exchange regime involving the 20 independent {Mo₉O₉} receptors of the capsule. Furthermore, quantitative analysis allowed determining the stability constants associated to the plugging process of the pores. Surprisingly, the affinity of the capsule for a series of cationic guests increases continuously with its apolar character as shown by the significant change of the stability constant from 370 to 6500 from NH₄⁺ and NEt₄⁺, respectively. Such observations, supported by the thermodynamic parameters evidence that the major factor dictating selectivity in the trapping process is mainly the so-called “hydrophobic effect”. Computational studies, using molecular dynamics simulations have been carried out in the conjunction of the experimental data. The analysis of the radial distribution functions g(r) reveals that NH₄⁺ and NMe₄⁺ ions behave differently in the vicinity of the capsule. The NH₄⁺ ions do not exhibit well-defined distributions in its close vicinity. In contrast, the NMe₄⁺ ions were identified as sharp distributions related to different scenario such as firmly trapped or as labile guest facing the {Mo₉O₉} pores. These conjugated experimental and theoretical insights should aid the exploitation of these giant polyoxometalates in solution for various applications.