In this review, we discuss selected topics which are relevant to implementing precision medicine in metabolic disorders. Personalization of diet and exercise may help in preventing obesity and type 2 diabetes (T2D). Weight loss should be personalized based on age, sex, ethnicity, and coexisting comorbidities. Advances in our understanding of the pathophysiology, genetics, and epigenetics of obesity promise to offer tailored management options. Careful risk assessment is necessary prior to intervention. Risk may be underestimated, e.g., in women, in different ethnic groups, and in people with T2D. More personalized approaches could be useful among persons who failed to respond to traditional risk factor management, such as pharmacological treatment for dyslipidemia and arterial hypertension. Nonalcoholic fatty liver disease/metabolic-associated fatty liver disease (NAFLD/MAFLD) is both a cause and an effect of altered glucose and lipid metabolism. Personalized medicine approaches could be key to identify more effective pharmacological strategies as well as to reverse this common and burdensome metabolic liver disease. Finally, metabolomics could be used to identify relevant biomarkers for cancer diagnosis, staging, and prognostication. Cancers of the colon and rectum, breast, prostate, thyroid, and ovaries illustrate the notion that cancer cell metabolic derangements may be utilized in clinical practice. A true personalization of pharmacotherapies should be pursued especially in obese patients with cancer.