This study investigates the feasibility of applying nano-SiO2 (NS) as interfacial bonding agents to realize robust bonds between normal-strength concrete and high-strength repair materials. Two nano-SiO2 application methods were experimentally investigated and compared: spraying the diluted solution and fabricating modified mortar-based adhesive agents. The effects of adopted measures and concentrations (0, 2.5, 3.75, and 5%) on interfacial bond performances were determined by slant shear, splitting bond, and water permeability tests. Finally, the underlying reinforcing mechanisms of each method were illustrated through a three-layer interface model and verified by SEM/EDS. The results demonstrated that the spray NS solution could produce compact C-S-H layers on substrate surfaces. However, the concentration should be strictly controlled (≤3.75%) to inhibit the locally over-concentrated phenomenon, which may result in porous microstructure and separation gaps at the interface. The synergetic effects between NS and mortar-based bonding agents considerably benefit interfacial cohesion and stress/deformation compatibility between overlays. Despite smooth interfaces, the optimal NS-modified mortar groups achieve equivalent slant shear strength to the surface textured samples. In addition, the failure mode of mortar groups turns into cohesive failure with the addition of NS. Compared to the control group, slant shear strength and impermeability of the S-W-3.75 and S-M-3.75 groups enhanced by 25.6%/7.5% and 118.4%/66.5%, respectively. In summary, fabricating NS-modified mortar is more effective in interface modification than spray treatments. The SEM/EDS results confirm that nano-SiO2 can diffuse in interfacial transition zones and refine the microstructure of corresponding layers. In particular, high proportions of Si atoms were also noted in the penetration layer of the substrate. Therefore, applying appropriate contents of nano-SiO2, especially incorporated into mortar-base bonding agents, is highly recommended in structural rehabilitation.