Components of aero-engine turbines are made with nickel-based superalloy, are subjected to complex thermo-mechanical loads. Creep-fatigue sequence of loading is one of the primary sequences of loading encountered in these engines, which will lead to failure in their components. The dominant mechanism due to creep-fatigue interaction (CFI) in nickel-based superalloys is multiple crack initiation and their propagation at high temperatures. Contemporary efforts to predict the mechanical response due to a combination of creep and fatigue loading, such as linear damage summation, use a procedure of combining damage estimations by creep and fatigue, in an arbitrary manner. The major drawbacks of these approaches are in terms of the extensive experiments required to estimate the model parameters and the limited predictive capability of these models. The combination of effects of creep and fatigue, as postulated in these models, are empirical and they do not seem to have any basis on the physics of deformation and failure in the materials. Such arbitrariness in combining the effects of creep and fatigue damages can be eliminated if the developed models are based on the mechanisms responsible for deformation and failure in these materials and the effects of these mechanisms are combined in some logical way. To address these issues, a thermodynamic-based unified mechanics theory (UMT) is proposed to capture the change in entropy due to creep and fatigue individually. An UMT-based model is used to monitor the degradation in the material due to a combination of these two types of loading, i.e., creep and fatigue, in nickel-based superalloys. The energy dissipated due to the hysteresis loop of CFI loading has been used to quantify entropy generation due to fatigue. The stress relaxation during hold time has been modelled using Norton's law of creep. The entropy generated and calibrated by these two loadings is combined using the framework of UMT, to predict the total damage in the material due to a combination of these two types of loadings. The predictions of the model are later combined with typical experiments conducted on these materials.