When machining high-speed steels (HSS) with micro-wire electrical discharge machining (micro-WEDM), high surface quality is achieved as standard. The value of the roughness parameter Ra is less than 0.2 μm. However, the problem is the performance of the electroerosion process (MRR), which is low. This problem is related to the mechanical and physical properties of the HSS in combination with the setting of the main technological parameters (MTP). The proposed solution to eliminate this problem relies on the selection of proper procedures for the determination of optimization criteria in relation to Ra and MTP, with the inclusion of properties of the machined material. The solution consisted in the identification of four significant physical (ρ, κ) and mechanical (Rm, HRC) indicators of HSS properties, on the basis of which a suitable combination of the process output parameters Ra and MRR can be determined through established mathematical regression models using simulation and optimization. In the next step, the proper values of the MTP output process parameter settings, which correspond to the optimized output parameters Ra and MRR during machining of HSS by micro-WEDM technology, were then obtained by the same approach.