This paper is concerned with the extension of a recently developed probabilistic framework based on Weibull’s weakest link and extreme-value statistics to aero-engine materials like titanium alloy and nickel-base super alloys using simulation strategies that capture both the essence of notch root stress gradient and the complexity of realistic microstructures. In this paper, notch size effects and notch root inelastic behavior are combined with probability distributions of microscale stress-strain gradient and small crack initiation to inform minimum life design methods. A new approach which can be applied using crystal plasticity finite element or closed-form solution is also proposed as a more robust approach for determining fatigue notch factor than the existing classical methods. The fatigue notch factors predicted using the new framework are in good agreements with experimental results obtained from literature for notched titanium alloy specimens subjected to uniaxial cyclic loads with various stress ratio.