One of the most common and important pathogenic bacteria is Staphylococcus aureus (S. aureus) which is known as a foodborne illness all over the world. The detection of micrococcal nuclease (MNase) can act as a unique diagnostic biomarker for the identification of S. aureus. So far, various complex methods have been introduced for the evaluation of S. aureus bacterium. However, they have different limitations such as labor-intensive, inaccurate results and time-consuming procedures. Thus, it is of particular attention to develop fast, easy, simple and more approachable detection methods based on nanotechnology and MNase detection. In this review, recent advances and modern techniques of ultrasensitive biosensors based on quantum dots (QDs), noble metal and magnetic nanoparticles (NPs), graphene oxide (GO) nanosheets, and also transfer energy strategy have been discussed for the identification of MNase activity and S. aureus contamination. Besides, advantages and disadvantages of different types of fluorescent, phosphorescent and colorimetric biosensors have been discussed.