Effective management of mycotoxins rely on stringent regulation and routine surveillance of food/feed commodities via efficient analysis, hence the continuous need for improved methods. The present study developed, optimized and validated a modified pressurized hot water extraction (PHWE) method for the simultaneous extraction of multi-mycotoxins from maize and subsequent quantification on LC-MS/MS. The PHWE system was modified using ethanol (EtOH) as a cosolvent, while a numerical modelling approach, the central composite design (CCD), was adopted for the optimization of the extraction conditions. Using the optimized method, it was possible to effectively extract and quantify 15 different mycotoxins from maize in a single step with satisfactory linearities (0.986-0.999), recoveries (14-124%) and other associated method validation parameters. Further efficacious application of the method to real samples re-affirmed the prospects of PHWE as a suitable, cost-effective and greener alternative to traditional methods of mycotoxin extraction.