International shipping’s particulate matter primary emissions have a share in global anthropogenic emissions of between 3% and 4%. Ship emissions of volatile organic compounds (VOCs) can play an important role in the formation of fine particulate matter. Using an aerosol box model for the near-plume scale, this study investigated how the changing VOC emission factor (EF) for ship engines impacts the formation of secondary PM2.5 in ship exhaust plumes that were detected during a measurement campaign. The agreement between measured and modeled particle number size distribution was improved by adjusting VOC emissions, in particular of intermediate-, low-, and extremely low-volatility compounds. The scaling of the VOC emission factor showed that the initial emission factor, based on literature data, had to be multiplied by 3.6 for all VOCs. Information obtained from the box model was integrated into a regional-scale chemistry transport model (CTM) to study the influence of changed VOC ship emissions over the Mediterranean Sea. The regional-scale CTM run with adjusted ship emissions indicated a change in PM2.5 of up to 5% at the main shipping routes and harbor cities in summer. Nevertheless, overall changes due to a change in the VOC EF were rather small, indicating that the size of grid cells in CTMs leads to a fast dilution.