The advent of next-generation sequencing (NGS) technologies, beginning with the commercial release of the 454 GS20 platform in 2005, revolutionized genomic research by exponentially reducing sequencing costs while dramatically increasing data output. This technological leap enabled large-scale genomic, transcriptomic, and metagenomic studies that were previously unattainable. In shrimp infectious disease research, early viral investigations—such as those involving infectious hypodermal and hematopoietic necrosis virus (IHHNV), Taura syndrome virus (TSV) and white spot syndrome virus (WSSV)—relied on traditional Sanger sequencing, as the scope of viral genomics was limited by lower data demands. However, the emergence of Acute Hepatopancreatic Necrosis Disease (AHPND), caused by Vibrio parahaemolyticus harboring a virulence plasmid carrying Photorhabdus insect-related (pirAB) toxin genes, marked a turning point. NGS became indispensable for the rapid identification, genome assembly, and molecular characterization of this novel pathogen and its virulence determinants. Furthermore, RNA-Seq has enabled in-depth analyses of host-pathogen interactions, revealing transcriptional responses during infection. Amplicon-based sequencing approaches, such as 16S rRNA profiling, have facilitated the exploration of microbial dysbiosis associated with complex diseases, uncovering interactions among microbial communities that may influence disease susceptibility and progression. This chapter reviews the evolution of NGS technologies and their application to shrimp infectious disease research. We also explore the future potential of long-read sequencing platforms (e.g., PacBio, Oxford Nanopore) and portable field-deployable sequencers (e.g., MinION), highlighting their promise for decentralized diagnostics and real-time, in situ pathogen surveillance and genomic characterization.