The article discusses the potential of combining circulating microRNAs (c-miRNAs) with cell-free DNAs (cfDNAs) and proteins as biomarkers for disease detection and monitoring. It highlights the advantages of c-miRNAs, including their stability, specificity, and non-invasive detection in biofluids. While cfDNAs and proteins are also promising biomarkers, they face challenges such as low sensitivity, variability, and limited specificity. The integration of c-miRNAs with these biomarkers could enhance diagnostic accuracy and enable earlier disease detection. The review emphasizes the need for standardized protocols and further validation studies to translate these biomarkers into clinical practice. It also discusses the challenges in detecting low-abundance proteins and the importance of multimarker approaches for more comprehensive disease analysis. The article concludes that c-miRNAs, due to their stability and tissue-specific expression, offer a promising solution for early disease detection and personalized treatment strategies.The article discusses the potential of combining circulating microRNAs (c-miRNAs) with cell-free DNAs (cfDNAs) and proteins as biomarkers for disease detection and monitoring. It highlights the advantages of c-miRNAs, including their stability, specificity, and non-invasive detection in biofluids. While cfDNAs and proteins are also promising biomarkers, they face challenges such as low sensitivity, variability, and limited specificity. The integration of c-miRNAs with these biomarkers could enhance diagnostic accuracy and enable earlier disease detection. The review emphasizes the need for standardized protocols and further validation studies to translate these biomarkers into clinical practice. It also discusses the challenges in detecting low-abundance proteins and the importance of multimarker approaches for more comprehensive disease analysis. The article concludes that c-miRNAs, due to their stability and tissue-specific expression, offer a promising solution for early disease detection and personalized treatment strategies.