An experimental investigation and numerical modeling using multiphysics finite element method were performed to study the thermal failure mechanism of low-profile quad flat package solder joints of memory module due to low-cycle fatigue. The strain, stress, and number of cycles to failure have been calculated according to a strain life Coffin–Manson and energy-based Morrow fatigue models. Scanning electron microscopy imaging at the end of thermal cycle was used to evaluate the damage initiation and propagation. The effect of the solder volume on fatigue life of solder joints was discussed. Through analyses of theoretical results and experimental data on fatigue life, cracks initiation and propagation have been highlighted and their possible causes have been discussed.