The phenomenon of synergistic improvement of the low-temperature rheology of waxy oil between asphaltenes and polymer pour point depressants has been widely reported. However, there has been limited systematic investigation into the variations in synergistic effects among different asphaltenes and pour point depressants. In this study, asphaltenes were extracted from crude oils originating from four distinct blocks, and their impacts on the low-temperature rheological and exothermic characteristics of undoped/doped model waxy oils were comprehensively examined. Furthermore, by integrating the results of mesoscopic particle size testing with the asphaltene molecular structure, we have unveiled the underlying mechanisms governing the synergistic modification effect between asphaltene and pour point depressants. The results indicate that the more pronounced the asphaltene's individual modification effect on waxy oil, the weaker its synergistic modification interaction with pour point depressants becomes. Delving into the underlying reasons, we postulate that the modification capability of asphaltene is intricately linked to its capacity to participate in the crystallization of wax components, with the content of methylene and heteroatoms in its molecule directly influencing its cocrystallization capacity with wax. However, simultaneously, the presence of nonpolar units in asphaltene molecules can disrupt the polar adsorption of PPDs on their surfaces, consequently diminishing the synergistic modification effect between asphaltene and PPDs. The discovery of this phenomenon contributes to the refinement of the theoretical framework governing the cooperative modification of waxy oil by PPDs and asphaltenes, offering insights into the subsequent targeted development of highly efficient pour point depressants for waxy crude oil.