This paper is aimed at identifying key microstructural parameters that play important roles in the failure initiation of polycrystalline subjected to creep and dwell loading. A finite element model, incorporating rate dependent elastocrystal plasticity, is developed for analyzing evolving variables in material microstructure. The crystal plasticity parameters are characterized by a combination of microtesting, orientation imaging microscopy, computational simulations, and minimization process involving Genetic algorithms (Ga). Accurate phase volume fractions and orientation distributions that are statistically equivalent to those observed in orientation imaging microscope scans are incorporated in the computational model of polycrystalline for constant strain rate, creep, and dwell tests. The computational model is used for the identification of possible microstructural variables that may result in local crack initiation. Basal normal stress, equivalent plastic strain, and stress in loading direction are considered as candidate parameters, of which the former is chosen as most probable from results of creep and dwell experiments and simulations. Creep induced load shedding phenomena is observed to lead to high value stresses that cause failure. The role of grain orientation with respect to the loading axis and misorientation with its neighbors, in causing load shedding and stress localizations is explored.