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 the ionic charge varies from 6- to 3- depending on the heteroatom, respectively, X = H₂ ²⁺, B³⁺, Si⁴⁺ or P⁵⁺. Titration experiments using complementary techniques (ITC, DOSY NMR, and electrochemistry) revealed that the affinity between γ-CD and polyoxometalates (POMs) is directly correlated to the charge density of the Keggin anion as reflected in the values of the binding constants K_1:1. 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, emphasizing 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 (K_1:1 > 10⁵ M⁻¹), but also the ability to interact with both CD faces resulting in a wide variety of supramolecular aggregates.