Metabolic and bariatric surgery (MBS) has long been considered the most effective long-term treatment for severe obesity and its associated comorbidities, including type-2 diabetes mellitus, metabolic syndrome, obstructive sleep apnea syndrome, and cardiovascular disease. Beyond weight loss, MBS has been associated with improved glycemic and metabolic control, lower apnea burden, reduced risk of major adverse cardiovascular events, and improved overall survival. In the last few years, the use of safe and effective weight-loss medications has revolutionized the management of patients with obesity, and may in the future influence referral patterns for MBS. Future research is therefore warranted to clarify the integration between MBS and these novel pharmacological opportunities, with the aim of optimizing patient selection and therapeutic pathways. The aim of this narrative review is therefore to describe the role of MBS in contemporary clinical practice, considering the evolving landscape of pharmacological approaches to treat patients with obesity.