The Hofmeister series has long been of both scientific and technological importance because it allows systematic predictions of the interaction between ions and molecules to be made. In this work, three different polyoxometalate (POM) anions and three different lipid monolayers were used to investigate the interplay between electrostatic and hydrophobic interactions. We used three Keggin-type POMs with different charges ([PW12O40]3–, [SiW12O40]4–, and [H2W12O40]6–) to eliminate any effects of morphology and to focus on the effects of the charge and hydrophobicity of the POM anions. The POMs adsorb onto cationic lipid monolayers via electrostatic interactions, while hydrophobic interaction is the dominant factor for adsorption onto anionic lipid monolayers when charge neutralization is provided by cationic counterions. In contrast, the dominant interactions experienced by zwitterionic lipid monolayers can switch between electrostatic interactions for POMs with higher charge density and hydrophobic interact...