There is an ever-expanding demand for inexpensive, rapid and reliable diagnostic sensor to simultaneously and accurately detect various biomarkers of clinical significance in human biofluids. Emergence of the powerful metallic nanozymes is the epitome of next-generation biomarker detection field. Such that in the past 7 years, researchers are fully leveraging their distinctive electrocatalytic features and versatility within multimodal and multiplexed detection systems. Multiplexed detection in a biosensor is substantial to diagnose diseases with numerous biomarkers through a small amount of biofluids.Multimodal readouts that combine various methods leads to enhance accuracy, sensitivity, cross-validation and real-time analysis of the targeted biomarkers. All of these components in a biosensor allow compact miniaturisation, microfluidic platform and integration of sensors with wearable technologies; which will further substantiate point-of-care diagnostics.This review explores numerous designs of metallic nanozymes, probes and signal amplification strategies applied in the ultra-selective and sensitive detection of multiple target biomarkers in the recent years. Overall, these innovations are collectively paving a route in the field towards a non-invasive, robust and efficient diagnostic platform tailored for personalised medicine and early disease detection.