The chaotropic character of Keggin-type polyoxotungstate anions was evaluated with respect to their ability to bind to γ-cyclodextrin (γ-CD) by varying the global charge density of the nanometer-sized polyanion. The strengths of the host-guest association were analyzed within the series of isostructural [XW12O40] n-anions where ionic charge varies from 6-to 3-depending on the heteroatom, respectively, X = H2 2+ , B 3+ , Si 4+ or P 5+. Titration experiments using complementary techniques (ITC, DOSY NMR, and electrochemistry) revealed that the affinity between γ-CD and the polyoxometalate (POM) is directly correlated to the charge density of the Keggin anion as reflected in the values of the binding constants K1:1. These constants increase dramatically following the order: [H2W12O40] 6-< [BW12O40] 5-< [SiW12O40] 4-< [PW12O40] 3-. Additionally, cloud point experiments on a non-ionic surfactant resulted in the same series of POMs emphasize the general affinity of these inorganic Keggin-ions to non-ionic organic soft matter due to a general solvent effect arising from the weakening of the hydration sphere with decreasing ionic charge. Furthermore, single crystal X-ray diffraction analysis showed distinct organizations of the POMs with γ-CD in the solid-state, where the moderate chaotrope [BW12O40] 5-interacts with the external wall of the γ-CD, while on the other side of the series, [PW12O40] 3-penetrates deeply into the cavity of the γ-CD through its secondary rim offering optimal contact area. Finally, our investigations revealed the unique behavior of [PW12O40] 3-, which displayed not only the highest affinity of the POMs to γ-CD (K1:1 > 10 5 M-1), but also the ability to interact with both CD faces resulting in a wide variety of supramolecular aggregates.