Hang Su, Xuyao Liu, Yuting Zhu, Tieshi Luowu, Huaiyuan Sun, Tongyue Zhang, Qi Shi, Shaoxiong Lu, Ben Zhang, Mei‐Lin Yang, Junchen Guo, Boya Shi, Zhaopei Guo, Xianying Meng, Jie Chen, Qiang Zhang
MicroRNAs (miRNAs), a class of short non-coding RNA molecules that are pivotal in post-transcriptional gene regulation, have emerged as invaluable biomarkers for the early diagnosis and therapeutic surveillance of critical diseases. However, their inherently low abundance and high sequence homology make detection through conventional modalities, such as quantitative polymerase chain reaction and microarrays, challenging. Recent advancements in nanomaterial-based biosensing have revolutionised miRNA detection, enabling ultrasensitive, multiplex, and real-time analyses. This review elucidates the biogenesis, regulatory mechanisms, and clinical implications of miRNAs and discusses nanomaterial-driven hypersensitive miRNA detection strategies for potential clinical precision medicine with emphasis on nanostructures that enhance signal amplification, specificity, and throughput while addressing the critical limitations of traditional detection methods. Future research should focus on the development of eco-friendly nanocomposites, artificial intelligence-driven data interpretation, and lab-on-a-chip devices for clinical diagnosis. By synergising nanoscale engineering with clinical demands, this review highlights the paradigm-shifting role of nanomaterials in promoting microRNA-based diagnostics in personalised healthcare and precision medicine. MicroRNAs as pivotal regulators link dysregulated expression to pathogenesis and progression of critical diseases. Nanomaterial-engineered biosensors overcome detection barriers through amplified signals and enhanced specificity for precision diagnostics. • MiRNAs are pivotal biomarkers for early disease diagnosis and therapy monitoring. • Nanomaterials enable ultrasensitive and multiplexed miRNA detection. • Nanomaterial classification into metallic, inorganic non-metallic, and organic biosensors. • Challenges include biocompatibility, scalability, and clinical translation hurdles. • Future trends: AI-driven analytics and portable biosensors for precision medicine.