We report on a mesoscale solubility reflecting the fact that solubility is achieved not only by the well-known "like likes like" or "like dissolves like" based on molecular solvation but also on mesoscale solubilization of dislike compounds characterized in that the solubility (homogeneous distribution over the whole volume of the system) is achieved on a mesoscale level ranging from tens to hundreds of nanometers. It is shown that mesoscale solubility is a spontaneously occurring, literally everywhere present phenomenon, which was hidden and overlooked for a long time. This paper reveals the physical mechanism of mesoscale solubilization comprising nucleation and aggregation accompanied by the development of significant surface zeta potentials on nanoprecipitates, giving them a long-term stability. We show that mesoscale solubilization is common for aqueous as well as nonaqueous systems. Experiments with organic solvents not capable of self-ionization (self-dissociation) instead of water also shed light on the mechanism of the generation of surface zeta potentials at hydrophobic interfaces. We identified the key parameters enabling the mesoscale solubilization and mapped its occurrence as their function. Mesoscale structures including their formation kinetics, long-term stability, and different types of solubilization procedures were characterized by scattering and ultramicroscopic visualization comprising sizing and counting.