AbstractDense packing is a universal tendency of organic molecules in the solid state. Typical porous crystals utilize reticular strong intermolecular bonding networks to overcome this principle. Here, we report a solvophobicity-based methodology for assembling discrete molecules into a porous form and succeed in synthesizing isostructural porous polymorphs of an amphiphilic aromatic molecule Py₆Mes. A computational analysis of the crystal structure reveals the major contribution of dispersion interaction as the driving force for assembling Py₆Mes into a columnar stacking while the columns are sterically salient and form nanopores between them. The porous packing is facilitated particularly in solvents with weak dispersion interaction due to the solvophobic effect. Conversely, solvents with strong dispersion interaction intercalate between Py₆Mes due to the solvophilic effect and provide non-porous inclusion crystals. The solvophobicity-directed polymorphism is further corroborated by the polymorphs of Py₆Mes-analogues, m-Py₆Mes and Ph₆Mes.