Magnetite nanoparticles (MNPs), with their distinct properties and controllability by using magnetic fields, have secured a central position in various industrial applications. Nevertheless, the surging demand for MNPs necessitates a meticulous examination of the sustainability of their production processes. This study embarks on a comprehensive evaluation of four case studies associated with the large-scale production of MNPs, specifically focused on environmental, economic, and exergy aspects. Our environmental assessment, employing life cycle assessment, revealed that the MNPs production using microfluidic devices (Case Study 4) showcased a promising environmental footprint. With the lowest electricity impact constituting only 8% of the overall environmental impact, it substantiates the efficacy of microfluidic devices in mitigating ecological repercussions. Economic analysis further reinforced the sustainability of Case Study 4. They exhibited superior financial viability, boasting a net present value of US$ 28,033,346, a modified internal rate of return of 19.73%, and a benefit−cost ratio of US$ 2.07. These figures underscore the economic robustness of this production methodology, suggesting an enticing prospect for large-scale MNP manufacturers. Finally, our exergetic evaluation demonstrated that Case Study 4 exhibited the least total exergy destruction, thereby displaying a superior thermodynamic efficiency. In summary, this study indicates that the adoption of microfluidic devices in MNPs production significantly enhances the environmental performance, economic feasibility, and energy utilization. These findings offer vital insights for those seeking to balance the demands of industrial production with sustainability objectives.