High-entropy alloys (HEAs) have attracted significant attention due to their unique properties, but their development is hindered by the vast compositional space requiring extensive experimentation. This study employs user-defined design response surface methodology (UDD-RSM) to optimize the processing parameters of a novel septenary equiatomic Ni-Al-Co-Cr-Cu-Mn-Ti HEA fabricated via mechanical alloying and spark plasma sintering (SPS). The effects of milling time (MT) and sintering temperature (ST) on microstructure, relative density, porosity, and microhardness were investigated. SEM-EDS analysis revealed a dominant CoNiCrCuMnTi phase with secondary CuNiMn and CrCo phases. The ANOVA results confirmed the significance of the developed quadratic models for predicting microhardness and relative density. The optimized model predicted that sintering at 896.009°C for 11.9 hours could produce a relative density of 99.994% and a microhardness of 742.019 HV. The study demonstrates the effectiveness of UDD-RSM in optimizing HEA processing parameters, contributing to the efficient development of these advanced materials with enhanced properties.