In this work, the conformer–rotamer ensemble sampling tool (CREST), with the underlying semiempirical GFN2-xtb method, was used for automated geometry exploration of the homodimers of pyrene, pyrene-4,5-dione, and pyrene-4,5,9,10-tetraone, along with the heterodimer of pyrene and pyrene-4,5,9,10-tetraone. Geometries and energies of the dimers were further refined at the ωB97X-D4/def2-TZVP level of theory, both in the gas phase and in toluene solution. Computations in solution were handled using the CPCM (conductor-like polarizible continuum model) and SMD (solvation model based on density) models. Two previously unidentified pyrene-homodimer conformations were identified, and the effects of oxidation on the geometries and energies of dimerization were explored; in general, oxidation leads to stronger intermolecular interactions and decreased solubility in toluene. For selected dimers, DLPNO-CCSD(T)/cc-pVTZ/SMD(Toluene) energies were determined at the DFT geometries and illustrated the accuracy of the ωB97X-D4 approach, with an MAD of 1.47 kJ/mol.