Electroporation is an effective approach for intracellular delivery of biomolecules; however, conventional systems are limited by their high voltage requirements, Joule heating, and nonuniform electric-field distribution. In this study, a microfluidic electroporation system based on hydrodynamic focusing and planar electrodes with a 40-µm gap was numerically designed. In the proposed design, the cell stream is confined near the bottom of the channel and guided toward the planar electrodes, enabling the generation of an effective electric field at low applied voltages. The geometry of the hydrodynamic focusing region was systematically optimized using a Taguchi design of experiments, together with ANOM and ANOVA analyses. Subsequently, three-dimensional hydrodynamic focusing, electric-field distribution, and Joule heating were evaluated under the optimized conditions. The results demonstrated that the proposed design can confine the cell stream to a region of approximately 20 × 20 µm² and generate electric-field strengths required for mammalian-cell electroporation at applied voltages below 1.75 V, while maintaining limited temperature rise due to Joule heating. These findings indicate that the integration of hydrodynamic focusing with reduced electrode spacing can provide an effective strategy for developing low-voltage, continuous-flow electroporation systems with improved control of electrical and thermal conditions. However, owing to the numerical nature of this study and the absence of experimental validation, the results represent a numerical feasibility assessment of the proposed design, and its biological efficacy requires experimental evaluation.