Nucleate boiling is an effective heat transfer mechanism. Previous studies have demonstrated that modifying surface structure or wettability can independently improve nucleate boiling efficiency; however, the combined effects and optimal modification sequence remain underexplored. This research aims to comprehensively analyze the influence of surface structure and wettability on the nucleate boiling heat transfer performance of refrigerants. Different surface structures and wettability were prepared using surface polishing, laser ablation, mechanical cutting, and a combination that involved initially employing laser ablation, followed by the application of chemical etching, and finishing with the treatment using materials possessing low surface energy. The static contact angles on these surfaces were measured via the capillary rise method, followed by pool boiling experiments and bubble behavior visualization. The results show that increasing surface wettability can enhance bubble departure frequency and capillary wicking, thereby improving critical heat flux and heat transfer coefficient. The key to optimizing surface modification to enhance critical heat flux involves constructing alternating high and low nucleation core regions to reduce interactions between bubbles; for enhancing heat transfer coefficient, the key lies in constructing compact nanoscale structures that expand the heat transfer and nucleation area, followed by improving wettability.