The effect of underfill material on reliability of flip chip on board (FCOB) assemblies is investigated in this study by using two-dimensional and three-dimensional finite element simulations under thermal cycling stresses from −55°C to 80°C. Accelerated testing of FCOB conducted by the authors reveals that the presence of underfill can increase the fatigue durability of solder interconnects by two orders of magnitude. Similar data has been extensively reported in the literature. It is the intent of this paper to develop a generic and fundamental predictive model that explains this trend. While empirical models have been reported by other investigators based on experimental data, the main drawback is that many of these empirical models are not truly predictive, and can not be applied to different flip chip architectures using different underfills. In the proposed model, the energy-partitioning (EP) damage model is enhanced in order to capture the underlying mechanisms so that a predictive capability can be developed. A two-dimensional finite element model is developed for stress analysis. This model accounts for underfill over regions of solder in an approximate manner by using overlay elements, and is calibrated using a three-dimensional finite element model. The model constant for the enhanced EP model is derived by fitting model predictions (combination of two-dimensional and three-dimensional model results) to experimental results for a given temperature history. The accuracy of the enhanced EP model is then verified for a different loading profile. The modeling not only reveals the influence of underfill material on solder joint durability, but also provides the acceleration factor to assess durability under life cycle environment, from accelerated test results. Experimental results are used to validate the trends predicted by the analytical model. The final goal is to define the optimum design and process parameters of the underfill material in FCOB assemblies in order to extend the fatigue endurance of the solder joints under cyclic thermal loading environments.