Accurate classification of two-phase gas-liquid flows is essential for reliable monitoring and control in industrial systems. Although several optical and machine-learning studies have been reported, most still focus on single wavelengths or isolated feature domains, lacking an integrated methodology that links sensor physics, feature extraction, and machine learning. This study addresses this gap by proposing the Multi-Feature Multi-Domain (MFMD) framework and its derived Optimal Feature and Method Selection (OFMS) guideline, providing a unified methodology to achieve high accuracy and model parsimony. The methodology was experimentally validated in horizontal air–water flows (five patterns: bubble, plug, slug, stratified, and wavy) using collimated near-infrared (NIR) sensors operating at 850, 980, and 1310 nm, selected for their distinct absorption sensitivities to interfacial, hybrid, and volumetric characteristics. Features were extracted from the time (Probability Density Function, PDF), frequency (Power Spectral Density, PSD), and time-frequency (Discrete Wavelet Transform, DWT) domains. This multi-domain feature set was processed by comparing feature selection (Recursive Feature Elimination, RFE) with transformation methods (Linear Discriminant Analysis, LDA, and Principal Component Analysis, PCA). Classification was performed using Support Vector Machine (SVM), k-Nearest Neighbors (kNN), Random Forest (RF), and Artificial Neural Networks (ANN). Results demonstrate that multi-wavelength fusion is essential for reliable flow discrimination. The RFE-based approach achieved 100% accuracy when combining all data sources, while supervised LDA significantly outperformed PCA by enhancing class separability. The resulting OFMS guideline consolidates these findings into a practical tool for selecting the most effective feature–classifier strategy, whether prioritizing maximum accuracy or a more parsimonious machine learning model.