<p>Vinasse, a byproduct of sugarcane bioethanol production, can harm the environment by polluting water bodies and emitting greenhouse gases. However, with proper treatment, vinasse can be converted into a valuable resource. This study explores its use in producing poly(hydroxyalkanoate)s (PHAs), focusing on optimizing the spray drying process with maltodextrin (MD) to improve manageability and shelf life. Using a Box-Behnken design, drying yields between 42.2 and 87.5% were achieved. Atomization air flow rate and maltodextrin concentration (expressed as percentage of the total solids content in the feed) were key factors, with optimal conditions identified at 156&#xa0;°C, 553&#xa0;L·h^− 1 air flow, 0.09&#xa0;L·h^− 1 liquid feed, and 49.7% MD concentration. Dried vinasse served as a substrate for <i>Bacillus megaterium</i> fermentations, yielding poly(3-hydroxybutyrate) (PHB) productivity from 0.0052 to 0.0285&#xa0;g·L^− 1·h^− 1, demonstrating the potential of vinasse and maltodextrin as effective carbon sources for sustainable PHB production.</p> Graphical Abstract <p></p>