Nanobiosensors represent a rapidly advancing class of analytical tools, offering high sensitivity, selectivity, and real-time detection across biomedical, environmental, and structural domains. This review synthesizes foundational quantum phenomena governing sensor response at the nanoscale and explores the integration of pH-responsive polymers to enhance specificity and functional adaptability. Key methodologies in nanobiosensor design and fabrication are examined, encompassing electrochemical, optical, piezoelectric, and field-effect transistor-based systems. Emphasis is placed on diverse applications, including early disease detection, real-time structural integrity assessment, and monitoring of environmental contaminants. Technical challenges such as material stability, signal drift, and manufacturing scalability are critically analyzed alongside emerging advantages such as multiplexing, miniaturization, and low power demand. A sustainable perspective is introduced through discussions on eco-friendly materials, life cycle assessment, and green fabrication processes. By consolidating recent advancements and interdisciplinary approaches, this work provides strategic insights for the development of next-generation nanobiosensors with enhanced performance, environmental compatibility, and translational potential.