In this research, a microstructure-based computational fatigue design model, named TMW model, is further studied by first using it to predict the fatigue crack nucleation lives of eight different alloys and steels, and comparing the predicted lives with that calculated values from the Coffin-Manson-Basquin relations which are obtained from experimental data fitting. Second, this model is improved by developing the mathematical expressions of the surface roughness factor in the TMW model in terms of the arithmetical mean deviation of the assessed profile which can be determined experimentally, thus making the TMW model more applicable. In addition, a microstructure-based finite element analysis model is created to investigate the effect of microstructural inhomogeneity on the fatigue crack nucleation life of nickel-based alloy Haynes 282. The TMW model shows effectiveness for predicting the fatigue crack nucleation life of structural materials.