A systematic analysis of the hydration structure of Cs+ ions in solution is derived from simulations carried out using a series of molecular models built upon a hierarchy of approximate representations of many-body effects in ion–water interactions. It is found that a pairwise-additive model, commonly used in biomolecular simulations, provides poor agreement with experimental X-ray spectra, indicating an incorrect description of the underlying hydration structure. Although the agreement with experiment improves in simulations with a polarizable model, the predicted hydration structure is found to lack the correct sequence of water shells. Progressive inclusion of explicit many-body effects in the representation of Cs+–water interactions as well as accounting for nuclear quantum effects is shown to be necessary for quantitatively reproducing the experimental X-ray spectra. Besides emphasizing the importance of many-body effects, these results suggest that molecular models rigorously derived from many-body ...