Systems and approaches for determining design of experiment parameters using largest empty area rectangle optimization for an injection molding system. The systems and methods include obtaining pressure versus time data sets indicative of fill step pressures and corresponding fill step times for a plurality of mold cycles and defining a low and high pressure versus time curves from the data sets, with the low and high pressure versus time curves being two surfaces of a geometric shape. The systems and methods further include identifying a top surface and a bottom surface of the geometric shape; identifying a rectangle having the largest area of all rectangles contained within the first geometric shape; and generating design of experiment parameters from the largest area rectangle.