The planar surface area and the spray nonuniformity are important parameters for determining spray evaporation characteristics. In this study, the effects of fuel compositions and two process variables (the injection pressure and axial distance from the measurement plane to the nozzle exit) on both planar surface area and spray nonuniformity were experimentally investigated via statistical extinction tomography. The design of experiment (DoE) was adopted to design the experiment procedure and analyze the data in a systematic way by establishing quadratic mixture models crossed with a linear process model. The planar surface area and the spray nonuniformity were calculated from spatial distributions of surface area density at three measurement planes, which were obtained by using an optical patternator SETSCAN OP-200. The results demonstrated that the axial distance had a significant influence on the planar surface area; whereas, the injection pressure did not show a definite trend for all the test fuels, yet the interaction between the injection pressure and fuel compositions played a noticeable role in determining the planar surface area. The spray nonuniformity was primarily influenced by injection pressure, while it exhibited little dependence on the axial distance. In general, the higher the injection pressure, the higher the spray nonuniformity would be. Fuel composition had an appreciable effect on the spray nonuniformity as well. The DoE-derived models were statistically significant according to analysis of variance analysis, and the optimal values in terms of planar surface area and spray nonuniformity were determined via numerical optimization.