More than four years have passed since an inimitable coronavirus disease (COVID-19) pandemic hit the globe in 2019 after an uncontrolled transmission of the severe acute respiratory syndrome (SARS-CoV-2) infection. The occurrence of this highly contagious respiratory infectious disease led to chaos and mortality all over the world. The peak paradigm shift of the researchers was inclined towards the accurate and rapid detection of diseases. Since 2019, there has been a boost in the diagnostics of COVID-19 via numerous conventional diagnostic tools like RT-PCR, ELISA, etc., and advanced biosensing kits like LFIA, etc. For the same reason, the use of nanotechnology and two-dimensional nanomaterials (2DNMs) has aided in the fabrication of efficient diagnostic tools to combat COVID-19. This article discusses the engineering techniques utilized for fabricating chemically active E2DNMs that are exceptionally thin and irregular. The techniques encompass the introduction of heteroatoms, intercalation of ions, and the design of strain and defects. E2DNMs possess unique characteristics, including a substantial surface area and controllable electrical, optical, and bioactive properties. These characteristics enable the development of sophisticated diagnostic platforms for real-time biosensors with exceptional sensitivity in detecting SARS-CoV-2. Integrating the Internet of Medical Things (IoMT) with these E2DNMs-based advanced diagnostics has led to the development of portable, real-time, scalable, more accurate, and cost-effective SARS-CoV-2 diagnostic platforms. These diagnostic platforms have the potential to revolutionize SARS-CoV-2 diagnosis by making it faster, easier, and more accessible to people worldwide, thus making them ideal for resource-limited settings. These advanced IoMT diagnostic platforms may help with combating SARS-CoV-2 as well as tracking and predicting the spread of future pandemics, ultimately saving lives and mitigating their impact on global health systems.