This review article, authored by Randa Abdel-Karim, provides a comprehensive overview of nanotechnology-enabled biosensors, covering their fundamentals, materials, applications, challenges, and future scope. The early sensing equipment used for measuring chemical, physical, or biological factors were large, inaccurate, and required manual interpretation. Nanomaterials such as nanoparticles, nanowires, carbon nanotubes (CNTs), nanorods, and quantum dots (QDs) are widely used in the production of nanobiosensors due to their unique properties, including color-changing ability, high detection sensitivity, large surface area, high carrier capacity, stability, and high thermal and electrical conductivity. The review highlights the wide range of clinically important molecules that can be detected by these sensing systems, including nucleic acids, viruses, bacteria, cancer antigens, pharmaceuticals, narcotic drugs, toxins, contaminants, and even whole cells in various media. The latest developments in nanobiosensors have significant potential for point-of-care diagnostics and early disease screening. The article discusses the principles of nanotechnology-enabled biosensors and their architectural design, including the classification of nanobiosensors, various attributes, and fabrication methods. It also broadens the reader's perspective on the materials used in biosensors and their potential applications. The review covers the different types of biosensors based on bioreceptors, transducers, technology, and detection systems, emphasizing the advantages and disadvantages of biosensors. Despite their potential, the transition from research to commercialization has been slow due to challenges such as biomaterial presence, sensor device development, and system integration. The high cost of biosensors is another significant obstacle to their widespread use.This review article, authored by Randa Abdel-Karim, provides a comprehensive overview of nanotechnology-enabled biosensors, covering their fundamentals, materials, applications, challenges, and future scope. The early sensing equipment used for measuring chemical, physical, or biological factors were large, inaccurate, and required manual interpretation. Nanomaterials such as nanoparticles, nanowires, carbon nanotubes (CNTs), nanorods, and quantum dots (QDs) are widely used in the production of nanobiosensors due to their unique properties, including color-changing ability, high detection sensitivity, large surface area, high carrier capacity, stability, and high thermal and electrical conductivity. The review highlights the wide range of clinically important molecules that can be detected by these sensing systems, including nucleic acids, viruses, bacteria, cancer antigens, pharmaceuticals, narcotic drugs, toxins, contaminants, and even whole cells in various media. The latest developments in nanobiosensors have significant potential for point-of-care diagnostics and early disease screening. The article discusses the principles of nanotechnology-enabled biosensors and their architectural design, including the classification of nanobiosensors, various attributes, and fabrication methods. It also broadens the reader's perspective on the materials used in biosensors and their potential applications. The review covers the different types of biosensors based on bioreceptors, transducers, technology, and detection systems, emphasizing the advantages and disadvantages of biosensors. Despite their potential, the transition from research to commercialization has been slow due to challenges such as biomaterial presence, sensor device development, and system integration. The high cost of biosensors is another significant obstacle to their widespread use.