In the digital transformation of global supply chains, the efficiency of in-plant logistics is substantially hindered by delayed information interactions. While in-vehicle personal digital assistants (PDAs) present a viable solution to these challenges, research on their effectiveness especially in dynamic environments, such as forklift operations, is overlooked. This study employed a VR-based simulation to assess the efficiency of manual data entry and retrieval for forklift operators using in-vehicle PDAs while driving. A controlled variable ergonomics experiment was conducted to evaluate operator’s performance during typical warehouse operations. The experiment used button size and button spacing on the PDA interface as independent variables, while task completion time, task completion accuracy, and driving safety were treated as the dependent variables. Data collected from 30 participants were analyzed using various statistical methods. Findings of the study indicate that the configuration of 25 mm button size and 0 mm button spacing outperformed other combinations in reducing human-computer interaction time, improving interaction accuracy, and enhancing driving safety. It is hoped that the results of this study will provide useful insights for the optimization of in-vehicle PDA interface design in in-plant logistics.