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The present study aimed to (i) select the most suitable solvent system for extraction of lycopene from industrial tomato waste; (ii) apply enzymatic pretreatment before extraction to improve lycopene recovery; and (iii) to optimize the process conditions for the selected enzyme and solvent combination using response surface methodology. Lycopene-rich oleoresins obtained through pretreatment of waste by a combination of cellulolytic and pectinolytic enzymes followed by ethyl acetate extraction had the highest phenolic compound concentration and improved antioxidant properties, as well as the highest lycopene recovery and one of the highest red color intensity. Optimized conditions were chosen to be as follows: enzymatic reaction temperature = 40 °C, enzymatic reaction time = 5 h, enzyme:substrate ratio = 0.2 ml/g, solvent:substrate ratio = 5 ml/g, extraction time = 1 h, enzyme:enzyme ratio = 1. Oleoresin with a concentration of 11.5 mg lycopene/g was obtained at the optimum conditions. Tomato paste production waste could be valorized to produce lycopene, a valuable ingredient for food and nutraceutical industries, by combined enzymatic and solvent extraction of the waste.