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Organ-on-a-chip (OOC) and organoid technologies are at the forefront of developing sophisticated in vitro systems that replicate complex host–microbiome interactions, including those associated with vaginal health and lung infection. We explore how these technologies provide insights into host–microbiome and host–pathogen interactions and the associated immune responses. Integrating omics data and high-resolution imaging in analyzing these models enhances our understanding of host–microbiome interactions' temporal and spatial aspects, paving the way for new diagnostic and treatment strategies. This review underscores the potential of OOC and organoid technologies in elucidating the complexities of vaginal health and lung disease, which have received less attention than other organ systems in recent organoid and OCC studies. Yet, each system presents notable characteristics, rendering them ideal candidates for these designs. Additionally, this review describes the key factors associated with each organ system and how to choose the technology setup to replicate human physiology.