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Introduction: The pressing need for rapid and sensitive diagnostic tools has driven innovation in nanobiosensors and smart microfluidic systems for Point-of-Care (POC) applications. The integration of advanced nanomaterials (such as graphene and nanoparticles) with microscale detection technologies has opened doors to highly specific in situ analysis of biomarkers for cancer and infectious diseases. However, although these Lab-on-a-chip (LoC) platforms represent the pinnacle of this new diagnostic generation, the transition of these advanced technologies from laboratory proof-of-concept to commercial success faces serious hurdles. Objectives: The main objective of this literature review is to identify LoC platforms already implemented in clinical practice, compare their efficacy with current reference methods, and critically analyse the main obstacles limiting their commercialization and widespread adoption. Methodology: A comprehensive search of the scientific literature was conducted for articles published between 2010 and 2026. A total of 49 articles were identified. Of these, 27 were excluded based on relevance criteria and 22 were included in this review.Results: Lab-on-a-chip (LoC) platforms and microfluidic devices offer significant advantages in various clinical areas, such as early cancer detection, infectious disease diagnosis, and fertility treatments, surpassing traditional methods in terms of speed and efficiency. However, their large-scale clinical adoption is still hindered by major challenges. Chief among these obstacles are the technological difficulties in integrating the chips with existing equipment and workflows, the economic and regulatory barriers linked to high production and commercialisation costs, and the negative environmental impact caused by the plastic waste from disposable devices. In summary, although this technology presents clear technical benefits, its global implementation depends on the ability to overcome these technological, economic, and environmental barriers. Conclusion: The true clinical impact of LoC technologies will depend on overcoming current manufacturing and interface barriers. The development of sustainable, low-cost alternatives, such as paper-based electrochemical biosensors, is a promising strategy not only to reduce environmental waste but also to democratise access to diagnostics in resource-limited settings and developing countries.