During the past two decades, with the fast development of various engineering fields, like aerospace, automobile, electronic device, etc., the demand for laser machining, especially ultrafast laser, is increasing, because of its high accuracy, high resolution and high efficiency. Based on the continuous technological breakthroughs of the laser devices, ultrafast laser technology quickly updates from picosecond to femtosecond or even attosecond for multiple machining cases, including high precision surface micromachining, 3D internal structuring, high-quality drilling, etc. Although laser machining technology is widely used in various application fields, the optimization and standardization of the related process parameters are far behind the research and renewal of the laser devices, especially for ultrafast laser, because most laser machining processes are quite complex with multiple parameters. It further leads to the compromises for the seemingly contradictory requirements of both efficiency and quality. Therefore, an integration concept combining the advantages of experiment, molecular dynamics (MD), artificial intelligence and high throughput optimization is proposed in this research to break the mutual exclusion between efficiency and quality in laser machining systems. In this concept, only tens of experimental samples are needed to form the datasets. Then MD model was established to provide more critical physical information, which can greatly help to reduce the data requirement of AI strategies. AI strategies further construct a quantitative link between idea MD model and actual processing parameters for laser machining. Finally, GA was used to quickly find the optimal solution set among thousands of alternative plans with multiple features. By integrating advantages of all the methods mentioned above, the comprehensive framework proposed in this research can be used to build the design system to make global optimization of the processing parameters precisely in a complex laser machining system. Therefore, this concept can help to quickly make precise process design for complex laser machining systems, so it can catch up with the update speed of the laser devices. This integrated optimization concept was further successfully applied to the process optimization of a new four-stage femtosecond laser drilling process, so as to improve the efficiency and quality of the drilling process at the same time. Finally, a validation was made for the four-stage percussion laser drilling plan for single crystal nickel-based superalloy to prove the reliability of this concept. The designed four-stage percussion laser drilling plan showed significantly improvement in both quality (taper degree and recast layer thickness) and efficiency, which can be directly used for machining the film cooling hole of the blade of aviation engine. Therefore, the concept can be used as an instructive method of breaking the mutual exclusion between efficiency and quality for laser machining, including femtosecond laser drilling.