Medium Density Fiberboard (MDF) has been one of the most rapidly growing composite panel products to enter world market in recent years. Optimization of drilling parameters for Medium Density Fiberboard (MDF) panel with multiple performance characteristics using Grey Relational Analysis (GRA) method was done. Drilling parameters, such as feed rate, spindle speed, drill diameters were considered for the study. By analyzing grey grade matrix, the degree of influence for each controllable process factor on to individual targets can be found. An optimal parameter combination of drilling operation was obtained via GRA. The feed rate was identified to be the most influencing factor on surface roughness and delamination. Additionally, ANOVA (Analysis of Variance) is used to find the interaction between parameters and the possible error in the experiments