Recently, 3D packaging has been regarded as an important technical means to continue Moore’s Law. However, excessive stacking will increase the longitudinal dimension, and one chip with high-density bondings packaging is still needed. Thus, it naturally places higher demand on thermal cycling reliability due to the decreased joint size to satisfy high-density packaging. In this work, the nano-Al2O3 (1 wt.%) modified Sn-1 wt.% Ag-0.5 wt.% Cu low-Ag solder was applied as a solder sample to evaluate the associated thermal cycling reliability. The investigated results revealed that the nano-Al2O3 modified solder did present enhanced thermal cycling reliability, as evidenced by the delayed microstructure coarsening and the inhibited atom inter-diffusion at interface caused by the adsorption of nano-Al2O3 on grain surfaces, and the resultant pinning effect. Worthy of note is that the potential of the newly developed nano-Al2O3 modified solder for high-density packaging applications (e.g., BGA, QFN, and CCGA) was evaluated based on the Finite Element Modeling.