Iron and steel factories in Egypt have been suffering from fine calcium oxide (CaO) emission which is considered as a waste and leads to many health hazards. An alternative, this waste (fine CaO) has been utilized as a low-cost, sustainable source of calcium sulfate impregnated sulfated silica (CSISS) nano-catalyst production. This hybrid catalyst has been utilized as a heterogeneous catalyst for biodiesel production from waste frying oil (WFO). In this study, the linear, quadratic and interaction effects of the main four factors that affect the biodiesel yield were investigated. An empirical model has correlated the experimental results and used to optimize and predict the biodiesel production yield. The model showed good agreement of about 93% with the experimental results and revealed that the optimum operating condition is: 50% SiO2 content, 20 min reaction time, 8:1 methanol to oil molar ratio and 3% catalyst weight at 55ºC and 300 rpm stirring speed to produce 99% biodiesel yield. The physicochemical properties of the produced biodiesel were analyzed. The combustion exhaust emissions of the produced biodiesel / petrodiesel blends have been evaluated. The techno-economic analysis elucidated that, the produced biodiesel is a strong competitor to petrodiesel with a cost of US$0.488/L.