<p>The growing concerns over fossil fuel depletion and engine emissions have motivated research into waste-derived and renewable fuel blends. Recently, a ternary blend consisting of 80% diesel, 10% plastic bag-derived oil, and 10% ethanol (D80P10E10) has been identified as a promising alternative due to its ability to enhance combustion and reduce fossil fuel dependency. However, optimization of injection parameters for this blend has not yet been explored in the literature, which is essential for a more holistic and practically viable implementation. This study investigates a common-rail-direct-injection (CRDI) engine fueled with D80P10E10, focusing on the optimization of injection parameters to achieve improved efficiency and lower emissions. Response Surface Methodology based on the Box–Behnken design was employed to model the effects of injection pressure (IP), injection timing (IT), and compression ratio (CR) on brake-specific fuel consumption (BSFC), exhaust gas temperature (EGT), and emissions of nitrogen oxide (NO_x), carbon monoxide (CO), hydrocarbons (HC), and smoke. The results of the analysis of variance confirmed that the developed models were statistically significant, with R² values ranging from 0.9856 to 0.9945. Optimization using the desirability function identified the best parameter combination as IP = 600&#xa0;bar, IT = 21.9⁰ bTDC, and CR = 16.5:1. Validation tests confirmed prediction errors below 3.25%. The optimized conditions lowered BSFC, CO, HC, and smoke, with a slight rise in NO_x. Overall, the results establish that optimization of injection parameters enables effective utilization of D80P10E10 in CRDI engines, offering a viable pathway for waste-to-fuel applications and sustainable diesel substitution.</p> Graphical abstract <p></p>