Thus, the metagenomics is a break-through in microbiology because now researchers can analyse raw genetic material from environmental samples instead of classical culturing. Finally, given the tremendous amount of work required to process metagenomic samples and generate meaningful data, a thorough understanding of these processes is essential for those contemplating a move into this research discipline. Herein, we compare different methods of DNA extraction for the best protocol that would result in high-quality genomic material from microbial communities. We examine next generation sequencing methods, including Illumina sequencing, PacBio long-read sequencing and Oxford Nanopore technologies for high-throughput genomic data. Choices for data processing, assembly, annotation and comparison of metagenomic datasets are discussed in detail in the chapter as well to highlight how bioinformatics analysis plays a key role in metagenomics. We also delve into the various applications of metagenomics for human health (e.g., microbiome and disease, and microbiome and wellness), environmental science (e.g., ecosystem health assessment methods, functional diversity techniques, and microbial interaction strategies), as well as biotechnology (e.g. enzyme discovery approaches; implementation in practical scenarios like native parasite controls, bioremediation options). At last, we discuss some of the limitations in metagenomic studies especially dubious output interpretation of data and reproducibility together with the ethical issues concerning data governing rules. Looking forward, we outline future directions in metagenomics and argue for combination of metagenomic data with other omics technologies such as transcriptomics and proteomics to provide a full portrait of microbial community structure/function relationships. This will be transformative in understanding microbial dynamics in health, industry and environmental sustainability.