Abstract Cytotoxic innate lymphoid cells, conventionally known as natural killer (NK) cells, play major roles in cancer immunity largely due to their natural cytolytic and immune regulatory functions. However, due to the extensive heterogeneity and plasticity seen among NK cells, their functions have yet to be fully harnessed in immunotherapy. The objective of this study is to elucidate NK cell diversity maturation, recruitment and effector function profiling in solid tumor microenvironments. We hypothesize that NK cells from different tissue locations display genetic and functional profiles that can predict NK effectiveness in solid tumor microenvironments. Here, we show the biological diversity that exists among NK cells from different locations pre- and post-interaction with solid breast cancer tumors, including heterogeneity of NK cell specific cluster of differentiation markers and gene expression perspectives based on flow cytometry, qPCR, RNA, and bioinformatics analyses. Understanding NK cells in the tumor microenvironment could help answer critical NK cell research questions and lead to advancements in cancer immunotherapy applications, ultimately helping to mitigate the cancer resources-results discrepancy.