Obesity now already becomes a critical health problem in our country and the world. Since the genomic and biochemical technology has developed in the era of precision medicine, great progression has been achieved in the field of obesity research and clinical practice. Obesity is considered to be a series of diseases with high heterogeneity beyond expectations, which brings up the challenges on its diagnosis and classification. Predictive models for obesity remain absent in clinical practice and commercial use. It is important to further understand the roles of gastric hormones and related molecules, proteins in feeding and reward system, as well as gut microbiota in obesity and associated diseases. The diagnosis and treatment of obesity require further progression in molecular biology and genetics with fruitful investigation of precision medicine, which might help the clinical translation in future.