Acute kidney injury (AKI) is a complex disease driven by the dynamic coupling of multiple pathological mechanisms. Current treatments remain primarily supportive, making it difficult to achieve precise regulation at key pathological junctures. In recent years, cell-derived nanomaterials (CdNMs) have demonstrated unique advantages in renal-targeted delivery, biocompatibility, and multi-mechanism synergistic regulation, due to their retention of the native biological properties of the source cells. This offers a novel technical pathway to overcome the limitations of traditional nanodelivery systems in AKI treatment. This review systematically summarizes the construction strategies and application progress of CdNMs-including exosomes, cell membrane-coated nanoparticles (CM-NPs), and engineered extracellular vesicles (eEVs)-with a focus on core AKI pathological processes. It further discusses their potential applications in multimodal synergistic therapy and integrated diagnosis-treatment approaches. More importantly, this review proposes a research paradigm in which the design principles of CdNMs are systematically coupled with AKI's pathological dynamics, therapeutic timing, and efficacy evaluation dimensions. This paradigm, driven by a reverse-engineering strategy from pathological mechanisms to material construction and functional assessment, provides methodological references for achieving precise intervention, predictable efficacy evaluation, and optimized clinical translation pathways for AKI.