Ti-6Al-4V, known for high strength to weight ratio and good resistance to corrosion, have been widely used in aerospace, biomedical, and high-performance sports fields. A wide range of physical and mechanical properties of Ti-6Al-4V can be achieved by varying the microstructures via deformation and recrystallization processes. The development of the shear band within alpha-TiAl has been widely reported and was found to play an important role in deformation and fatigue behaviors of Ti-6Al-4V. In this study, crystal plasticity constitutive relations are developed to model the mechanical deformation behavior of Ti-6Al-4V while considering the shear localization phenomena triggered by the planar slip under static or quasi-static loading at room temperature. Both strain gradient and shear enhancement model can be used to simulate the formation and evolution of shear bands. This study will focus on the more robust shear enhancement model for its simplicity in application. The fatigue indication parameters (FIPs) are proposed to account for the different crack formation mechanisms in Ti-6Al-4V. The cyclic and fretting fatigue sensitivity to microstructure and loading parameters in dual phase Ti-6Al-4V are investigated. The aim of this study is to establish a completed microstructure-scale fatigue analysis approach that can be applied in the engineering applications such as fretting fatigue.