<p>Postoperative Nausea and Vomiting (PONV) is a potential complication in all people undergoing general anesthesia (GA), causing significant discomfort and potentially leading to serious complications. Despite decades of research and the implementation of various preventive drugs and measures, complete prevention via traditional guidelines continues to pose challenges in clinical settings. This article will review mechanisms, influencing factors (including patient-related, surgery-related, and anesthesia-related factors), and strategies for prevention and treatment, both pharmacological and non-pharmacological, for PONV in adultsunder GA. This manuscript also summarizes randomized trials investigating the incidence of PONV in adults receiving opioid-sparing or opioid-free perioperative GA-based protocols. This review aims to summarize evidence-based guidance amidst traditional guidance, and other recent considerations, for optimizing anesthetic management strategies in clinical practice.</p>