The human skin surface harbors a complex ecosystem in which epidermal cells, resident microbiota, and surface metabolites cooperate to maintain a stable barrier against external stressors. Disruption of host or microbial metabolism at this interface is closely associated with impaired epidermal barrier integrity and the development of localized skin diseases. Such conditions can drive microbial dysbiosis and metabolic imbalance, leading to altered skin physiology and pathological manifestations. These changes arise from abnormal host secretions, including those from sebaceous glands, sweat glands, and keratinocytes, and are further shaped by shifts in microbial communities and their metabolites. This review focuses on microbial metabolic activity at the skin surface, examines disease-associated changes in the cutaneous metabolic microenvironment, and critically evaluates the physiological and translational relevance of microbiota-derived metabolites. By systematically elucidating the interactions among the skin barrier, skin microbiota, and surface metabolites, we further assess the translational potential and current limitations of microbiome-derived metabolites and microbiome-based interventions.