Through targeted spray applications, precision agriculture can provide not only environmental benefits but also lower production costs, improving farm competitiveness. Nevertheless, few studies have focused on the cost-effectiveness of precision agriculture sprayers in vineyards, which are among the most widespread specialty crops. Therefore, this is the first study that aims to evaluate the cost-effectiveness of variable rate technology (VRT) and unmanned aerial vehicle (UAV) sprayers compared to a conventional sprayer in a hypothetical and representative vineyard area of southern Italy. The economic analysis, based on technological parameters in the literature, enabled the identification of the minimum farm size (break-even point) for introducing precision agriculture sprayers (PAS), considering the annual cost of the pesticide treatments (equipment and pesticide costs). Our findings revealed that the UAV sprayer—if permitted by law—could be the most convenient option for farms larger than 2.27 ha, whereas the VRT sprayer should be chosen by farms over 17.02 ha. However, public subsidies, such as those provided by the Italian Recovery Plan, make adopting VRT sprayers also economically viable for areas as small as 3.03 ha. Finally, the sensitivity analysis confirmed that the purchase price and pesticide cost are the most sensitive parameters affecting the break-even points. Our findings shed light on the economic sustainability of these innovative sprayers, a key driver for their adoption by farmers and for setting future strategies for facing the current agricultural crisis.