The advent and widespread application of next-generation sequencing (NGS) technologies to the study of microbial genomes has led to a substantial increase in the number of studies in which whole genome sequencing (WGS) is applied to the analysis of microbial genomic epidemiology. The whole-genome sequencing (WGS) or whole-exome sequencing (WES) are the most appropriate strategy for human genomics in a clinical or research environment. These approaches bring many benefits as the amount of information delivered aids discovery and increases our understanding of the interactions between genetics and human health. As a biological system analytical technique, the same is also visibly useful in genotypes of plant kingdom. Application of next-generation sequencing (NGS) to the study of clonal, slowly evolving microorganisms such as Mycobacterium tuberculosis (MTB) via whole genome sequencing (WGS), has led to improvements in epidemiological tracking of outbreaks, and aids in clarifying transmission patterns that cannot be confidently resolved using conventional locus-based genotyping methods. Indeed, the decreasing cost and increasing accuracy, efficiency, resolution, and reproducibility of NGS technologies have made large-scale WGS of target organisms, not only feasible for basic research, but also applicable for surveillance and response activities in cases of living organisms of both self and cross-fertilized or clonal reproduction systems. However, to maximize the utility of this technology, consideration of the possible biases and limitations of the experimental methodology employed based on population structure, genic behavior including relationships and their control patterns. There is an ongoing debate in the community regarding the most cost-effective strategy, not just for the actual sequencing but also for the effects on the health care system. A small panel allows for the development of assays that more adequately test the full sequence of the specific genes. It is important to note that the extent of knowledge of the genes implicated in a disease needs to be understood. If only a small percentage of the genetics is accounted for then a WES approach is likely to prove more successful. Furthermore, knowledge of potential sequencing biases is necessary to ensure that appropriate downstream analytical tools, models, experimental variables and statistical methods are appropriately utilized. There are many factors that need to be considered when selecting the most appropriate approach to a gene sequencing project. WGS is a very powerful tool, but the cost of such an approach appears to have stopped falling. A targeted approach is often a more suitable and cost-effective alternative, especially for clinical and specific clinical research use. As our knowledge of the genetics implicated in diseases increases, the need to use a broad net to detect mutations in a limited subset of genes lessens and so gene panels will become the way forward. However, there are many considerations to take into account before deciding whether WGS, WES, or a more targeted approach using gene panels is the right solution, such as experimental aim, cost, time to results, and data analysis and management. Data analysis and management is an area that is often overlooked in the decision-making process. Elaborate support of Mr. Aqief of ASRBC in the preparation of the note is highly appreciated. Prof. Lutfur Rahman