The construction of accurate constitutive equations is critical for the reliability analysis of the solder joints in high-density interconnect. However, there are some distinct differences between the actual solder joints and conventional bulk solder in determining the parameters for constitutive equations. In this work, the Young's modulus and hardness of various grain regions are experimentally investigated using electron backscatter diffraction and nanoindentation for the Sn-3.0Ag-0.5Cu polycrystalline and single-grain solder joints. The disparities in the Young's modulus and hardness of different grain regions in the polycrystalline solder joint are up to 25.11% and 28.34%, respectively, while those of the single-grain solder joint exhibit stability. It indicates the anisotropy of β-Sn grains and the size effects between actual solder joints and bulk solder materials. Furthermore, a method is proposed to determine the parameters of the Anand constitutive equations using high-temperature nanoindentation creep data. A flip-chip assembly in thermal shock conditions is numerically investigated. The Darveaux model is employed to predict the thermal fatigue life of the critical solder joint. Compared to experimental results, the life prediction of the solder joint using nanoindentation is found to be accurate. A concept of life correction factor n has been proposed to improve the accuracy of the predicted life.