Structure–property correlation is an important aspect in crystal engineering which has direct applications in the development of pharmaceutical solid dosage forms. In this manuscript, we present a combined structural, thermal and computational study of seven new cocrystals and cocrystal solvates of an antipsychotic drug, olanzapine, with three coformers (hydroquinone, resorcinol and catechol) and attempt to understand the effect of solid-state molecular packing on the thermal properties (desolvation and melting behaviour). The cocrystals were designed by utilizing the robust hydrogen-bonded synthons between the drug and coformers, while the cocrystal solvates were obtained by the isostructural replacement of toluene in a previously reported multicomponent structure by benzene, xylene and ethyl benzene. The positional variations of hydroxyl groups in coformer molecules had a remarkable influence on the crystal packing of cocrystals. The olanzapine–hydroquinone (OLZ–HQ) combination in 1 : 1 stoichiometry crystallized as cocrystal solvates that was attributed to the persistent formation of rectangular hydrogen-bonded grid networks with inherent hydrophobic cavities for aromatic guest molecule inclusion. In contrast, the olanzapine–resorcinol (OLZ–RES) and olanzapine–catechol (OLZ–CAT) combinations in 1 : 1 stoichiometry resulted in non-solvated cocrystals and can be classified as pharmaceutical cocrystals. The desolvation patterns of cocrystal solvates were explained based on the structural similarities and dissimilarities, host–guest interactions, void types (closed vs. open), void size (narrow and wide), packing coefficients and boiling points of the guest molecules. Solid-state DFT calculations were performed to assess the desolvation energies, stabilization energies of desolvated systems and lattice energies of all cocrystals and cocrystal solvate systems and the results were correlated with the experimental observations. The solvent molecules play an important role in the structure stabilization, rendering the crystal lattice of the OLZ–HQ structure energetically feasible and compensating for the loss of packing density rather than simply occupying the void space in the crystal structure. The large melting point differences and thermal stabilities of two anhydrous cocrystals (M.P. of OLZ–RES is 196 °C and M.P. of OLZ–CAT is 135 °C) were also explained on the basis of packing coefficients and lattice energy calculations.