In the present study, a Box–Behnken design of response surface methodology (RSM) was employed to optimize the processing factors (force: 100, 150, and 200 kN; speed: 3, 5, and 7 mm/min; and temperature: 40, 60, and 80 °C) for extracting pumpkin seeds oil under uniaxial compression. The design generated 15 experiments including twelve combinations of factors and three replicates at the center point. The responses: oil yield (%), oil expression efficiency (%), and energy (J) were calculated, and the regression models determined were statistically analyzed and validated. The optimum factors combination: 200 kN, 4 mm/min and 80 °C predicted the oil yield of 20.48%, oil expression efficiency of 60.90%, and energy of 848.04 J. The relaxation time of 12 min at the optimum factors increased the oil efficiency to 64.53%. The lower oil point force was determined to be 57.32 kN for estimating the maximum oil output. The tangent curve and generalized Maxwell models adequately (R2 = 0.996) described the compression and relaxation processes of pumpkin seeds oil extraction. Peroxide value increased with temperatures. The study provides detailed information useful for processing different bulk oilseeds under uniaxial loading for optimizing the mechanical oil pressing in large-scale oil production.