Laser micromachining has become an essential tool in precision manufacturing due to its non-contact nature, high spatial resolution, and capability to produce intricate micro-features. However, identifying the optimal combination of process parameters remains challenging because of the nonlinear and interdependent effects of laser power, scanning speed, and pulse frequency on cut quality. In this study, a comparative framework is presented that benchmarks the Taguchi Design of Experiments (DoE) against a Deep Neural Network (DNN) model to predict and optimize the micromachining performance of stainless steel. A unified Cut Quality Index (CQI) was developed by combining three critical responses kerf width, heat-affected zone (HAZ), and edge chipping into a single measure of overall cut integrity. A physics-consistent dataset of 75 samples, comprising 20 literature-based and 55 synthetically generated data points, was constructed to ensure both experimental realism and statistical diversity. The Taguchi analysis using an L18 orthogonal array identified the optimal parameters as 80 W laser power, 250 mm/s scanning speed, and 60 kHz pulse frequency, corresponding to the highest signal-to-noise ratio and thermally balanced operation. The DNN model achieved strong predictive accuracy (R² ≈ 0.92–0.94), effectively capturing nonlinear parameter interactions without overfitting. The results demonstrate that while the Taguchi method efficiently identifies robust process windows with minimal experimentation, the DNN extends predictive capability across continuous, untested regions of the process space. Collectively, these findings establish a physics-informed, data-driven comparative framework for intelligent optimization of laser micromachining, with direct relevance to aerospace, biomedical, and precision micro-engineering applications.