Background: This work proposes a hypothetical model that integrates human factors (e.g. inherent ability and acquired expertise) and task factors (e.g. pre-procedural data, visual and haptic information) to better understand the hand ergonomics adaptation needed for optimal safety and efficiency during simulated brain tumor resections. Methods: Hand ergonomics of neurosurgeons, residents and medical students were assessed during simulated brain tumors resection on the NeuroVR virtual reality neurosurgical simulation platform. Spatial distribution of time expended, force applied, and tumor volume removed, and other metrics were analyzed in each tumor quadrant (Q1 to Q4). Results: Significant differences were observed between the most favorable hand ergonomics condition (Q2) and the unfavorable hand ergonomics condition (Q4). Neurosurgeons applied more total force, more mean force, and removed less tumor per unit of force applied in Q4. However, total volume removed was not significant between the two quadrants indicating hand ergonomics adaptation in order to maximize tumor removal. In comparison, hand ergonomics of medical students remained unchanged in all quadrants, indicating a learning phenomenon. Conclusions: Neurosurgeons are more capable of adapting their hand ergonomics during simulated brain tumor resections. Our proposed hypothetical model integrates our findings with the literature and highlights the importance of experience in the acquisition of adaptive hand ergonomics.