In this study, a unified formulation is derived for fatigue crack nucleation under general unbalanced cyclic loading profiles, and it is combined with the integrated creep-fatigue theory (ICFT) to give a physics-based theoretical description from very low cycle fatigue to high cycle fatigue, rather than building up by empirical rules. Using several engineering alloys as illustrative examples, the model has been shown to effectively include the effects of mean stress /ratcheting strain, and monotonic plastic damage in metal fatigue. For small-amplitude loading cases, it works equivalently well as the SWT model, but it goes beyond the empirical data-collapsing method to predict fatigue life based on the material basic physical/mechanical properties such as the elastic modulus, Poisson’s ratio, surface energy, Burgers vector without the need of data regression. Therefore, it offers a unified tool for fatigue design and analysis.