The present study investigates the effects of four controllable variables on the metallurgy and geometry of acute (30 degrees to surface) laser percussion drilled holes in 2 mm thick flat pieces of nickel superalloy: CMSX-4. Design of experiment (DOE) and statistical modelling were used in the experimental study to understand parameter interactions. Assist gas pressure, nozzle stand-off distance, focal plane position (FPP), and number of pulses were chosen as the independent process variables. A central composite design (CCD) was chosen as it offered the most economical number of experiments for the required information. The response surface method (RSM) was used to develop three models. The significant factors in each model were identified based on the analysis of variance (ANOVA), and the models were checked by complete residual analysis. It was found that a high FPP and high nozzle stand off gave the minimum entrance oxide layer thickness whereas the recast layer was minimized for a zero FPP and high pulse number.