Hydrophobic interactions are often explored in solution-state aggregation of molecules. However, an experimental electron density description about these interactions is still lacking. Here, we report a systematic study on the electronic nature of methyl···methyl hydrophobic interactions in a series of multicomponent crystals of biologically active molecules. Charge density models based on high-resolution X-ray diffraction allow the visualization of subtle details of electron density features in the interaction region. Our study classifies these interactions as atypical group···group interactions in contrast to σ-hole interactions, which are stabilized by the minimized electrostatic repulsion and maximized dispersion forces. For the first time, we quantified the solid-state entropic contribution from the torsional mode of the methyl groups in stabilizing these interactions by thermal motion analysis based on neutron diffraction as well as variable-temperature crystallography. The carbon atoms in methyl···methyl interactions show a unique upfield chemical shift in the 13C solid-state NMR signal.