The reliability of lead-free solder joints on flexible printed circuit board (PCB) has created significant new challenges in the industry, especially in automotive electronics, and possibly for future wearable electronics. In the automotive industry, thermal cycling test and random vibration test need to be conducted to certify every electronic product to be used in harsh automotive environments. In order to accelerate the testing time, we may need to subject the electronic components, in particular, sensors to both loadings such as thermal cycling and vibration. During all the experiments, the electrical signals of each specimen were continuously monitored by using an event detector. One advantage of this method is that any individual soldering interconnect failure will result in the diagnostic signal of the circuit, which could be detected in real-time. A simulation was used to confirm the possibility of the stress concentration location caused by the vibration and thermal cycling loads. The influence of vibration frequency and acceleration on the vibration fatigue life of solid joints was investigated. In this paper, the submodeling technique was used to construct the finite element model of the rigid-flexible printed circuit board (rigid-flexible PCB) coupled with a MEMS pressure sensor subjected to temperature cycle and random vibration loadings. The research results are helpful to effectively characterize the performance of the MEMS sensors under both thermal cycling test and vibration test. Two kinds of land shapes and two kinds of PCB assemblies were selected. In order to investigate the crack growth in the solder joint, the solder joint is sliced and the crack on the cross section of the solder joint was observed. Results of finite element modeling analysis were consistent with the experimental results. Two design parameters have been identified in our research as being important to soldering usage in automotive environments: pad type (teardrop versus nonteardrop) and pad size (big versus small, matching size for Cu-wire and pad). Experimental results also showed that the solder joint with a big land shape presented a relatively good thermal fatigue resistance.