<p>Thin-film nanocomposite (TFN) membranes have received significant attention because of their excellent separation performance, structural flexibility, and tunability. As the demand for high-efficiency membrane technologies in industry grows, it becomes imperative to transition TFN membranes from lab-scale prototypes to commercial-scale production. This review critically discusses the materials, fabrication strategies, and application domains of TFN membranes, focusing specifically on scalability and large-scale viability. We first examined polymeric and ceramic substrates in terms of their mechanical properties, chemical compatibility, and scalability. Next, we evaluated various nanomaterials, based on their physicochemical characteristics, performance advantages, and economic considerations. Industrial applications were then systematically reviewed, covering water desalination, organic solvent purification, heavy metal recovery to gas separation. Next, eight key fabrication methods, such as interfacial polymerization (IP) and the doctor blade technique, were compared, emphasizing their scalability and technological readiness, with focus on both the flat sheet and the hollow fiber configuration. A simplified comparative economic assessment, based on standardized metrics ($/m²) and representative literature and industrial data, was also presented to provide a preliminary comparison of material costs and economic competitiveness relative to conventional membranes. Finally, the review outlined current challenges, such as occupational nano safety and equipment complexity, and projected future directions, including integrating artificial intelligence (AI) to streamline nanomaterial design and process optimization. This comprehensive review provides a roadmap for advancing the scalable fabrication and practical deployment of TFN membranes in environmental and energy applications.</p>