A volume-of-fluid (VOF) finite volume model under the ANSYS® Fluent framework was coupled with the response surface method (RSM) to find the best operating conditions within a jettability window for two selected responses in a drop-on-demand inkjet printing process. Twenty-five runs were generated using a face centred design and numerical simulations were carried out using viscosity, surface tension, nozzle diameter, and inlet velocity as input factors. A mesh study was first conducted to establish the necessary number of cells to best combine accuracy and expended time. Selected runs were discussed, identifying the underpinning mechanisms behind the droplet generation at different time periods. Each one of the responses was evaluated under different input factors and their effects were identified. Finally, the desirability function concept was advantageously used to proceed with a multiple optimization where all the responses were targeted under usual jettability/printability conditions.