This work investigates the wear behavior of nickel-based alloy during ultrasonic vibration-assisted machining (UVAM) by combining molecular dynamics simulation and thermodynamic theory. The research reveals that the tangential force exhibits periodic variations during UVAM, with a period half of the vibration period. Tangential force and total resistance decrease due to the synergistic effect of vibration-induced softening and thermal softening. A deeper understanding of the total resistance variation during the UVAM process can be achieved by the dimensionless resistance coefficient, which is difficult for the traditional friction coefficient (CoF). The Bejan number elucidates the contributions of the thermal softening and vibration-induced softening effects in the wear process. The findings highlight that the vibration-induced softening effect dominates when adjusting the amplitude for the active control of friction. In contrast, when the frequency is modulated, the contributions of vibration-induced softening and thermal softening effects are nearly equivalent. Furthermore, the wear mode transitions with increasing vibration frequency, characterized by the Strouhal number (Srw). The vibration wear mode attains dominance when Srw > 1.88. This work provides essential theoretical guidance to gain insight into the wear behavior in UVAM to optimize the machining performance.