Organic crystallization controls natural and pathological processes and technologies to produce pharmaceuticals, fine chemicals, and electronic and optical devices. In contrast to water-based crystallization, the interactions and structures that govern crystallization from organic solvents remain elusive. We characterize the thermodynamics of crystallization of etioporphyrin I from five solvents selected to highlight the roles of several solute–solvent interactions; etioporphyrin I represents a class of molecules that arrange in low-symmetry crystals suitable for semiconductors and solar panels. To understand solvent structuring at the crystal interface and solvent–solute interactions in the solution, we employ as molecular probes the crystallization enthalpy and entropy, complemented by UV–vis absorption spectra of the solutions and electron microscopy and X-ray characterization of the crystal phases. The enthalpy and entropy trends reveal that solvent structuring insignificantly affects the solution thermodynamics owing to the weak solvent–solvent bonds. London dispersion forces between nonpolar groups of the solute and solvent take the place of the hydrophobic interactions common in aqueous solutions and, directed by attraction between permanent dipoles, dominate the solute–solvent interactions. Surprisingly, both hydrogen bonds and salt bridges contribute little to the solution thermodynamics. The emerging insight into the fundamental interactions in organic solutions illuminates the search for crystallization solvents that optimize the numbers, morphologies, and sizes of crystals of organic materials with appealing properties.