Anti-fatigue design in the machining process of aviation material requires advanced processes to enhance the surface integrity and a holistic model which can optimize the process aiming at maximum fatigue life. In the present study, the axial ultrasonic assisted milling process was utilized to machine the Inconel 718 while the process executes the thermomechanical cutting and peening action simultaneously. To optimize the process factors, a hybrid model using a combination of regression analysis and an analytical model was developed to correlate the machining factors, i.e., vibration amplitude, cutting velocity and feed rate to fatigue life. Herein, the former was used to map the process inputs to surface integrity aspects (SIAs), viz. roughness, hardness and residual stress; then, the SIA was mapped to fatigue life through a stress-based approach. The obtained results revealed that there is close agreement between the measured and predicted values of fatigue life where the prediction error is less than two times the dispersion. On the other hand, applying ultrasonic vibration at the highest amplitude together with the maximum feed rate and cutting velocity yield significant improvement in fatigue life, i.e., three times the same condition without ultrasonic vibration in light of the enhancement of compressive residual stress and work hardening of the surface layers.