Current ablation strategies for persistent atrial fibrillation (AF) remain suboptimal, with success rates around 50%. Pulmonary vein isolation (PVI) serves as the cornerstone of ablation, yet adjunctive strategies have shown inconsistent results in randomized controlled trials. This review critically examines the outcomes and limitations of these approaches while identifying key barriers to success, including incomplete understanding of AF mechanisms, patient heterogeneity, technical challenges in achieving durable lesions, and the absence of standardized procedural endpoints. A novel electro-anatomically guided ablation protocol is proposed, integrating advanced mapping techniques and procedural endpoints aimed at achieving AF termination. Furthermore, it discusses emerging technologies such as pulsed field ablation (PFA), which hold promise for enhancing safety and long-term outcomes. These insights provide a framework for future research and the optimization of persistent AF ablation strategies.