Modern gas turbine engines provide large amounts of thrust and withstand severe thermal-mechanical conditions during the load and mission operations characterized by cyclic transients and long dwell times. All these operational factors can be detrimental to the service life of turbine components and need careful consideration. Engine components subject to the harshest environments are turbine high-pressure vanes and rotating blades. Therefore, it is necessary to develop a turbine component three-dimensional life prediction system, which accounts for mission transients, anisotropic material properties, and multi-axial, thermal-mechanical, strain, and stress fields. This paper presents a complete life prediction approach for either commercial missions or more complex military missions, which includes evaluation of component transient metal temperatures, resolved maximum shear stresses and strains, and subsequent component life capability for fatigue and creep damage. The procedure is based on considering all of the time steps in the mission profile by developing a series of extreme points that envelop every point in the mission. Creep damage is factored into the component capability by debiting thermal-mechanical accumulated cycles using the traditional Miner’s rule for accumulated fatigue and creep damage. Application of this methodology is illustrated to the design of the NASA Energy Efficient Engine high pressure turbine blade with operational load shakedown leading to stress relaxation on the external hot surfaces and potential state of overstress in the inner cold rib regions of the airfoil.