Hydration-shell vibrational spectroscopy provides an experimental window into solute-induced water structure changes that mediate aqueous folding, binding, and self-assembly. Decomposition of measured Raman and infrared (IR) spectra of aqueous solutions using multivariate curve resolution (MCR) and related methods may be used to obtain solute-correlated spectra revealing solute-induced perturbations of water structure, such as changes in water hydrogen-bond strength, tetrahedral order, and the presence of dangling (non-hydrogen-bonded) OH groups. More generally, vibrational-MCR may be applied to both aqueous and nonaqueous solutions, including multicomponent mixtures, to quantify solvent-mediated interactions between oily, polar, and ionic solutes, in both dilute and crowded fluids. Combining vibrational-MCR with emerging theoretical modeling strategies promises synergetic advances in the predictive understanding of multiscale self-assembly processes of both biological and technological interest.