As one of the advanced manufacturing technologies, high-speed five-axis ball end milling has been widely used in high-end manufacturing fields because of its high efficiency, high quality, and high precision. Based on the analysis of cutting effect and response surface methodology, a series of experiments were carried out. Based on geometric modeling and numerical simulation, various tool postures are comprehensively analyzed, and the down milling process combining positive tilt angle and positive lead angle can achieve better cutting effect. The variance and interaction of the important factors affecting the surface integrity and the cutting process were analyzed, and the polynomial equations reflecting the relationship between the processing index and the input process variable were obtained. Finally, a process optimization schemes with various optimization criteria were proposed. When using a larger tilt, smaller fz and higher spindle rotation speed for multi-objective optimization, a combination of a smaller ap and a smaller ae, or a combination of a larger ap and a smaller ae is advantageous to result in high ideality. The combinations of large lead, large tilt, and high spindle speed give full play to the advantages of high-speed cutting technology. The process optimization plan will help determine the processing strategy for achieving the desired machining results and better surface quality based on actual application requirements. Finally, the future research areas are prospected for the high-performance machining technology.