Global demand for animal protein has increased dramatically due to the exponential development of the human population, which in turn led to intensification of aquaculture. However, the aforementioned fact impose stress on cultivable organisms, resulting in susceptibility to infectious diseases. Alternatively, this situation warranted the search for an environmentally friendly approach to replace the application of various chemical, physical, and biological processes that fail to cope with the required standards. In this context, biofloc technology (BFT) has emerged as a viable technique for aquaculture management with a sustainable and environmentally benign approach that has proven to have no adverse effects. BFT provides a conducive environment for cultivable aquatic species and system sustainability. Also, by maintaining the C:N ratio, the microbiome of BFT offers an appropriate carbon source and recycles waste. As well, the addition of probiotics and prebiotics (polysaccharides) in BFT certainly improves the host's antioxidant status, innate immunity, and disease resistance. Numerous studies on the use of BFT for various aquatic farmed species have been carried out recently, and it has evolved as a promising technique for the growth of sustainable aquaculture. BFT uses less water, increases productivity, provides biosecurity, and improves the health status of numerous aquaculture species. This review aims to compile and validate the scientific data about the benefits of biofloc in ensuring the health, biosecurity, and sustainability of aquaculture in light of the transformative role of probiotics, prebiotics, and microbiomes.