Abstract This article presents a time-efficient method to optimize the positions of film cooling holes on a gas turbine blade's squealer tip for cooling and aerodynamic performance. A computational approach is employed for the optimization, including validations against experiments. Five discrete film cooling holes are considered, and two different blowing ratios of 0.4 and 1.0 are studied. The positions of cooling holes on the tip along the tangential direction are varied as the input parameters of optimization. The multi-objective optimization uses an algorithm with an artificial neural network for fast fitness function predictions. The best cooling configuration found by the optimization achieves a 13.43% reduction in total heat flux and a 0.4% increase in aerodynamic loss when the blowing rate is 1.0. Including the casing relative motion in the computations results in a total pressure loss coefficient increase of about 8% for both blowing ratios. For M = 1.0, imposing the casing's motion results in a 10.2% reduction in total heat transfer to the tip compared to the stationary casing. For the lower blowing rate of 0.4, the total heat flux reduction to the tip is 12.0% because of the imposed casing motion. Hence, the cooling effectiveness can be improved by employing the particular position optimization method presented in this study. The results suggest that experimental and computational heat transfer studies on cooled turbine blade tips, especially in cascade arrangements, need to consider the relative motion of the blade tip.