Diabetic retinopathy (DR) is increasingly recognized as a complex neurovascular degenerative disorder driven by intertwined immune and metabolic disturbances within the retinal microenvironment. Chronic hyperglycemia induces metabolic stress, mitochondrial dysfunction, and oxidative imbalance, which, in turn, activate innate and adaptive immune pathways. Key mechanisms-including complement dysregulation, microglial activation, leukostasis, cytokine and chemokine signaling, and advanced glycation end-product-mediated inflammation-contribute to endothelial injury, barrier breakdown, and progressive neuronal loss. Parallel alterations in lipid metabolism, amino acid utilization, and mitochondrial bioenergetics further amplify inflammatory cascades and shape the retinal immune landscape. This review synthesizes current evidence on how immune-metabolic crosstalk orchestrates early and late stages of DR, integrating findings from transcriptomic, proteomic, metabolomic, and epigenetic studies. We examine core signaling hubs that couple metabolic dysfunction to inflammatory amplification, including complement components, the advanced glycation end product (AGE)-receptor for AGE (RAGE) pathway, cytokine networks, and immune response regulation. Adopting a systems biology perspective, we highlight how convergent mechanisms can unify vascular, neuronal, and glial pathology under a shared framework of immune-metabolic imbalance. An extensive literature search was conducted (PubMed, accessed December 2025). By positioning DR as a model of inflammatory retinal degeneration, this review outlines a conceptual foundation for network-based diagnostics and therapeutics. Understanding the dynamic interactions among immune signaling, metabolic stress, and neurovascular instability may inform future strategies to restore retinal homeostasis and prevent vision-threatening disease progression.