Obesity is a complex systemic condition with significant sexual dimorphism, increasing the risks of disorders such as type 2 diabetes mellitus, arterial hypertension, dyslipidemia, metabolic dysfunction-associated steatotic liver disease, chronic kidney disease, premature cardiovascular disease, and certain types of cancers. A recent publication by Christaki et al. on the comprehensive overview of obesity management in Innovative Medicines and Omics highlights the multifactorial nature of obesity, as well as the importance of lifestyle changes, alongside pharmacological treatments and bariatric surgery. This commentary advocates for precision medicine strategies to effectively address the challenges posed by obesity. By highlighting the potential health and economic benefits of reducing obesity, we call for a holistic approach that integrates behavioral, medical, and policy interventions. We also identify research gaps, suggesting that future studies explore endocrine connections in obesity and assess endoscopic techniques targeting the duodenum as adjunct therapies in the context of tailored care.