The loading capacity of a drug carrier is determined essentially by intermolecular interactions between drugs and carrier materials. In this review, the process of drug loading is described in detail based on the differences in the driving force for drug incorporation, including hydrophobic interaction, electrostatic interaction, hydrogen bonding, Pi-Pi stacking and van der Waals force. Modifying drug-loading sites of carrier materials with interacting groups aiming at tailoring drug-carrier interactions is reviewed by highlighting its importance for improving in vitro properties such as the loading capacity, release behaviour and stability. Other factors affecting drug loading, methods employed to predict the encapsulation capacity and the techniques to verify intermolecular interactions are also discussed to inform the readers of all-sided information on drug-loading processes and theories. The drug carriers can be designed more reasonably with the better understanding of the nature and interacting mechanism of intermolecular interactions.