To reduce reflective cracking in asphalt pavements, gravel base layers are commonly employed to disperse stress and delay structural damage. However, the loose nature of gravel bases results in complex interlayer contact conditions, typically involving interlocking between gravel particles in the base and aggregates in the asphalt surface course. In order to accurately simulate this interaction and to improve the interlayer shear performance, a mesoscale finite element model was developed and combined with macroscopic tests. Effects due to the type and amount of binder material, type of asphalt surface layer, and external loading on shear strength were systematically analyzed. The results indicate that SBS (Styrene–Butadiene–Styrene)-modified asphalt provides the highest interlayer strength, followed by SBR (Styrene–Butadiene Rubber)-modified emulsified asphalt and unmodified base bitumen. SBS (Styrene–Butadiene–Styrene)-modified asphalt achieves optimal interlaminar shear strength at a coating rate of 0.9 L/m². Additionally, shear strength increases with applied load but decreases with increasing void ratio and the nominal maximum aggregate size of the surface course in the analyzed spectra. Based on simulation and experimental data, an equivalent macro–meso predictive model relating shear strength to key influencing factors was established. This model effectively bridges mesoscale mechanisms and practical engineering applications, providing theoretical support for the design and performance optimization of asphalt pavements with gravel bases.