The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) represents a continuously evolving pathological process in which renal interstitial fibrosis serves as the central nexus. This review synthesizes current evidence and delineates the major pathogenic axes that drive fibrosis, including amplification of the NOD-like receptor family pyrin domain containing 3 (NLRP3)–Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κB)/Signal Transducer and Activator of Transcription 3 (STAT3) inflammatory cascade, sustained activation of the renin–angiotensin system (RAS), maladaptive tubular epithelial repair with G2/M cell-cycle arrest, endothelial injury and microvascular rarefaction leading to hypoxia-inducible factor (HIF) signaling, mitochondrial dysfunction with impaired autophagy, cellular senescence with a senescence-associated secretory phenotype (SASP), multiple programmed cell-death pathways, and epigenetic alterations involving DNA methylation, histone modifications, and miR-21/29/200 networks. A key innovative finding of this review is the identification of temporally defined intervention windows in the AKI–CKD continuum. Early intervention targets inflammation and oxidative stress suppression; the intermediate phase focuses on transforming growth factor-β (TGF-β) and RAS-mediated fibrogenesis, while promoting adaptive repair; the late phase aims to restore tissue homeostasis through anti-senescence and regenerative strategies. This approach shifts from generalized treatment strategies to personalized, stage-specific therapies in renal fibrosis. Representative interventions—including ACE inhibitor (ACEI)/angiotensin receptor blocker (ARB) therapy, Roxadustat, mesenchymal stem cells and extracellular vesicles, and senolytic regimens—are discussed with regard to their mechanisms and optimal timing. Barriers to clinical translation, such as patient heterogeneity, lack of reliable biomarkers for early fibrosis detection, and discrepancies between preclinical models and clinical endpoints, are also highlighted. The integration of predictive modeling, multi-omics, and spatial transcriptomics is essential for refining individualized intervention windows, advancing precision strategies to prevent or attenuate AKI–CKD progression.