AbstractReported is the hydration of nanomicelles in the gas‐phase using spectroscopic methods and quantum chemical calculations. A fine‐tuning of the experimental conditions allowed formation of a propofol trimer and tetramer with a water molecule and to determine the structure of the aggregates. Their electronic and IR spectra were obtained using mass‐resolved laser spectroscopy, together with the number of conformational isomers for each stoichiometry. Interpretation of the spectra in the light of high‐level calculations allowed determination of the cluster’s structure and demonstration that the trimer of propofol with a water molecule forms cyclic hydrogen‐bond networks but, on the other hand, the tetramer is big enough to encapsulate the water molecule inside its hydrophilic core. Furthermore, these hydrated nanomicelles present an unusually high binding energy, thus reflecting their high stability and their capability to trap water inside.