Nurse scientists play an important role in studying complex relationships among human genetics, environmental factors, and the microbiome, all of which can contribute to human health and disease. Therefore, it is essential that they have the tools necessary to execute a successful microbiome research study. The purpose of this paper is to highlight important methodological factors for nurse scientists to consider when designing a microbiome study. In addition to considering factors that influence host-associated microbiomes (i.e., microorganisms associated with organisms such as humans, mice, and rats), this manuscript also highlights study designs and methods for microbiome analysis. Exemplars are presented from nurse scientists who have incorporated microbiome methods into their program of research. This review is intended to be a resource to guide nursing-focused microbiome research and highlight how study of the microbiome can be incorporated to answer research questions.