Synergistic effects of oxidation on high temperature isothermal and thermo-mechanical fatigue behavior are studied. Experiments were conducted under different strain-temperature variations and atmospheres to reveal the varying severities of oxide induced failure. Conditions conducive to integranular creep damage under thermo-mechanical fatigue are identified, and the competing damage mechanisms are classified for steels, Ni-based superalloys, and Al alloys. Requirements and a solution procedure are outlined for a thermo-mechanical fatigue life prediction model which is then applied to 1070 steel. MarM-247 nickel-based superalloy, and Al2xxx-T4 aluminum alloy.