This study revisits and expands the field of lactam cocrystals to include addnl. structural analogs of sulfonamides and evaluates the potential of virtual screening methods.Cocrystn. of lactams is driven by both lactam-lactam and lactam-API interactions.Four cocrystals, SA/CLCC, SG/CLCC, DDS/CLCC-I, and DDS/CLCC-II, were exptl. produced, including two novel ones, SG/CLCC and DDS/CLCC-II.The structures of the new multicomponent phases were successfully solved using powder X-ray diffraction data complemented by DFT-d calculationsCalorimetric anal. confirmed that DDS/CLCC-II is the high-temperature polymorph and is enantiotropically related to DDS/CLCC-I.Virtual screening methods, including mol. complementarity, multicomponent hydrogen-bond propensity, and mol. electrostatic potential maps, demonstrated utility but were limited by the mol. properties of the chosen coformer class.Crystal structure prediction on the other hand proved to be the most reliable computational approach, successfully identifying cocrystn. outcomes in all three systems and matching the exptl. 1:1 cocrystal structures with computationally generated ones.The exptl. investigations revealed that cocrystn. could reduce, but not completely prevent, the sublimation tendency of ε-caprolactam.Solubility tests showed no improvement in API solubility, as the cocrystals disintegrated into their individual components within the shortest time of contact with water.Thus, this work sheds light on lactam cocrystn., highlighting the strengths and limitations of current predictive approaches, as well as the challenges that need to be addressed in exptl. work.