A systematic search method that identifies trial crystal structures by manipulating a molecular model in direct-space within a defined unit cell and comparing calculated and experimental powder X-ray data and assessing calculated lattice energies has been extended to allow simulation of crystal structures having two symmetry-independent molecules within the unit cell. Overall, the methodology developed is composed of three components: first, identification of all isolated molecular-adducts that are viable in terms of intermolecular pair energy calculated using an atom-atom approach; second, clustering of all similar adducts through energy minimization and ranking of the predicted structures; third, treatment of the best molecule-pair adducts identified in a systematic search of all possible intermolecular packing arrangements. The validity of the approach, is demonstrated via its application to predict the crystal structures of cocrystals of urea with the isomers of dihydroxy benzene (catechol, resorcinol, and hydroquinone).