Understanding the nature of non-covalent interactions (NCIs) between asphaltene molecules is not only theoretically interesting but also important for practical application. We performed quantum chemical calculations to reveal the configuration feature and intermolecular interaction characteristics of asphaltene dimers using three representative asphaltene model compounds and their derivatives. The frontier molecular orbitals and electrostatic potential map of the model asphaltenes were analyzed to reveal the nature of interaction between the asphaltene monomers. The calculation of binding energies indicates that the stability of asphaltene dimers not only depends upon the number of aromatic rings but also relies on the presence of heteroatoms in the aromatic core and aliphatic side chains, which could change the electrostatic charge distribution on the molecular van der Waals surface. In addition, NCIs and the natural bond order analysis method were used to identify the interactions that promote the formation of asphaltene dimers. It was found that the reduced density gradient isosurfaces could clearly reveal the type of interactions between two asphaltene monomers in their dimers. The results indicate that various interactions possess either an electrostatic or a dispersive nature, including hydrogen-bonding, θ–θ, θ–π, and π–π interactions, among which the π–π stacking interaction is believed to be the major driving force for asphaltene aggregation.