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Obesity is a growing global epidemic, contributing to major health conditions such as cardiovascular disease (CVD), stroke, type 2 diabetes mellitus (T2DM), and cancer. The purpose of this review is to evaluate and compare obesity management strategies, with a focus on the magnitude of weight loss achieved and the adverse effects associated with each intervention. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure methodological rigor in study selection and reporting. Bariatric surgery is currently considered the most effective intervention for achieving significant and sustained weight reduction, particularly in patients with severe obesity. Procedures such as Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and adjustable gastric banding consistently demonstrate superior weight loss and metabolic improvements compared with nonsurgical therapies. However, surgery carries well-documented risks, such as gastric strictures, anastomotic leaks, thromboembolic events, infections, and the need for reoperations. Long-term challenges include nutritional deficiencies, GI complications, and, in some patients, partial weight regain. Pharmacologic options are increasingly important adjuncts or alternatives to surgery. Novel agents, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), have gained popularity due to their substantial efficacy among pharmacological options, favorable safety profile, and non-invasive nature. Other agents, including phentermine-topiramate (PHEN-TPM), naltrexone-bupropion, and orlistat, also play roles in individualized treatment plans, although weight loss outcomes are typically more modest than with surgical approaches. In conclusion, a multimodal strategy integrating surgical and medical therapy may provide the most durable results. This approach not only enhances weight loss but also supports long-term maintenance and optimizes management of obesity-related comorbidities.