Cells constantly engage with diverse microbial populations that inhabit the human body, collectively known as the microbiome. These microorganisms, including bacteria, viruses, and fungi, interact dynamically with host cells, influencing tissue behavior, metabolic processes, and immune regulation. This review discusses the multifaceted interactions between cells and microbiomes, highlighting the molecular signals, metabolic exchanges, and regulatory feedback loops that sustain tissue integrity and promote repair. We also explore the role of microbial metabolites in stem cell regulation, inflammatory modulation, and neuronal activity, emphasizing the significance of microbial balance for cellular homeostasis. The integration of these insights has implications for regenerative medicine, tissue engineering, and the development of microbiome-informed therapeutic strategies.