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The gut-lung axis links early-life microbial programming to long-term respiratory health, offering a pivotal framework for understanding childhood asthma pathogenesis. This review synthesizes current evidence on how disruptions in microbial-immune crosstalk during critical developmental windows shape asthma susceptibility. Perinatal determinants-including maternal diet, delivery mode, antibiotic exposure, and breastfeeding-establish gut microbial communities that educate the developing immune system. Distinguishing itself from recent reviews, this review offers three novel contributions: (i) an integrated multi-omics framework linking early-life microbial maturation trajectories to specific asthma endotypes; (ii) a systematic synthesis of the molecular mechanisms by which microbial metabolites-including short-chain fatty acids, tryptophan derivatives, and bile acids-orchestrate gut-lung immune crosstalk; and (iii) a clinically actionable precision medicine algorithm that translates multi-omics profiling into personalized risk prediction, endotype-driven therapy selection, and targeted preventive strategies. Dysbiosis, characterized by delayed microbial maturation and depletion of short-chain fatty acid-producing taxa, compromises epithelial barrier integrity and skews immune homeostasis toward pro-allergic type-2 responses. Microbial metabolites, particularly short-chain fatty acids (acetate, propionate, butyrate) and tryptophan derivatives (indole-3-lactic acid, indole-3-propionic acid), serve as key molecular mediators that regulate regulatory T cells differentiation, reinforce mucosal barriers, and modulate distal airway inflammation. Microbial signatures correlate with specific asthma endotypes, offering opportunities for patient stratification. We critically evaluate emerging microbiome-targeted interventions-including strain-specific probiotics, prebiotics, postbiotics, and fecal microbiota transplantation-highlighting both therapeutic promise and the need for rigorous, well-powered clinical trials. Integrating multi-omics microbial profiling with host genetics and clinical phenotyping holds potential for microbiome-informed precision medicine, enabling personalized risk prediction, endotype-driven therapy selection, and novel preventive strategies targeting the gut-lung axis from the earliest stages of life.