The skin is the interface between the human body and the environment, and the different features in distinct skin regions, such as different temperatures, humidity levels, gland densities, and pH values, create a variety of niches that can support a diverse skin microbiome. This microbiome includes bacteria, archaea, viruses, fungi, and even mites. A healthy skin microbiome helps maintain skin homeostasis, protects against pathogens, communicates with and trains the immune system, and affects wound healing. However, the skin microbiome can be influenced by many factors, including intrinsic factors like aging and extrinsic factors like cosmetic. Recent advances in molecular biology techniques and next-generation sequencing have drastically increased our understanding of the microorganisms that live on our skin, but the microbes are often still difficult to culture and study. Researchers are continuing to optimize strategies such as 3D skin modeling, skin microbiota transplantation, and prebiotic and probiotic supplementation in order to reveal how the microbiota can be manipulated to improve skin health. Given the numerous associations between skin microbiome disruption and skin disorders, further fine-tuning of microbe isolation and manipulation methods, although challenging, could help experts develop and apply strategies to combat skin diseases and aging.