The premise of disease-related phenotypes is the definition of the counterpart normality in medical sciences. Contrary to clinical practices that can be carefully planned according to clinical needs, heterogeneity and uncontrollability is the essence of humans in carrying out health studies. Full characterization of consistent phenotypes that define the general population is the basis to individual difference normalization in personalized medicine. Self-claimed normal status may not represent health because asymptomatic subjects may carry chronic diseases at their early stage, such as cancer, diabetes mellitus and atherosclerosis. Currently, treatments for non-communicable chronic diseases (NCD) are implemented after disease onset, which is a very much delayed approach from the perspective of predictive, preventive and personalized medicine (PPPM). A NCD pandemic will develop and be accompanied by increased global economic burden for healthcare systems throughout both developed and developing countries. This paper examples the characterization of the suboptimal health status (SHS) which represents a new PPPM challenge in a population with ambiguous health complaints such as general weakness, unexplained medical syndrome (UMS), chronic fatigue syndrome (CFS), myalgic encephalomyelitis (ME), post-viral fatigue syndrome (PVFS) and chronic fatigue immune dysfunction syndrome (CFIDS).