<p>Immunoglobulin A nephropathy (IgAN), the most prevalent primary glomerulopathy globally, exhibits intricate pathomechanisms and significant clinical heterogeneity, with up to 50% of patients progressing to kidney failure within 20 years. Contemporary management of IgAN combines causal therapy against pathogenic galactose-deficient immunoglobulin A1, including enteric budesonide with symptom-oriented interventions via renin-angiotensin system inhibitors to mitigate hypertension, glomerular hyperfiltration, proteinuria, and cardiovascular sequelae. Nevertheless, suboptimal treatment efficacy observed in 20–30% of patients with IgAN implies the existence of additional pathogenic mechanisms beyond current therapeutic targeting. Emerging evidence underscores the pivotal role of metabolic checkpoints—central regulatory hubs governing glucose, lipid, amino acid, and mitochondrial networks—in driving a self-perpetuating pathogenic loop linking metabolic reprogramming and immune dysregulation in IgAN. Mechanistically, hypoxia-driven stabilization of hypoxia-inducible factor 1-alpha hyperactivates aerobic glycolysis, fueling T helper 17 cell/T regulatory cell imbalance and mesangial proliferative injury. Peroxisome proliferator-activated receptor dysfunction exacerbates lipotoxic damage and fibrosis. Indoleamine 2,3-dioxygenase 1- and arginase 1-mediated amino acid metabolic disturbances disrupt immune homeostasis. Meanwhile, mitochondrial oxidative stress, coupled with maladaptive unfolded protein response, propagates tubular injury through reactive oxygen species-mediated NOD-like receptor family pyrin domain containing 3 inflammasome activation and epigenetic dysregulation. Interventions targeting metabolic checkpoints, including sodium-glucose cotransporter 2 inhibitors, mechanistic target of rapamycin inhibitors and peroxisome proliferator-activated receptor-γ agonists demonstrate promising renoprotective effects in IgAN preclinical models and early-phase trials, heralding the era of dual metabolic-immune precision therapeutics. However, it is critical to emphasize that these emerging strategies currently constitute a hypothesis-generating framework and must be validated in future large-scale, randomized controlled trials with adequate power and follow-up before clinical application. Future research should integrate multi-omics and single-cell analysis to delineate metabolic heterogeneity and develop renal-targeted nanodelivery systems for endotype-based precision medicine. This paradigm shift will guide IgAN mechanism exploration and management, transitioning from conventional immunosuppression to metabolic-immune synergy regulation.</p>