The transdiagnostic approach to psychopathologies was introduced as a solution to high comorbidity and weak differentiation of psychological disorders. Factor analytic studies have revealed a hierarchical structure with the highest single p-factor (i.e., psychopathology), which parallels the results in the personality studies of general factor of personality over the Big 5 dimensions. The etiology of the single super-factor is considered in the life history strategy in evolutionary psychology. Two strategies to clinically utilize the p-factor are discussed, as follows: (1) setting the p-factor as a predictor to probe the relevant mediators (i.e., endophenotype) of symptoms and (2) moving across the levels of hierarchy to enhance flexible responding. The final topic discussed is the cybernetic principle with goal hierarchy, which will enhance studies on personality, psychopathology, and well-being.