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Engineering biomaterials that actively interface with and instruct their biological milieu have given rise to a new generation of platforms for tissue repair and companion diagnostics. Among them, aerogel scaffolds, with their ultra‐porous architecture, ultralow density, tunable mechanics, and versatile chemistries, have emerged as transformative candidates capable of emulating and interpreting extracellular environments. This review highlights up‐to‐date advances shaping the landscape of aerogel‐based scaffolds in tissue repair and diagnostic applications. We first summarize emerging fabrication and assembly strategies, including sol–gel processing, freeze‐drying, electrospinning, and 3D printing, which unlock hierarchical morphologies and bioinspired features. The recent implementations of intelligent aerogels for tissue repair and neuroregeneration are then highlighted, together with related applications in bioactive functionalization, immune modulation, wound healing, sustained drug delivery, and moist repair dressings. Meanwhile, we outline aerogel‐based disease diagnosis regarding genotypic physiological cues, focusing on faithfully detecting nucleic acids, tumor biopsy, virus antigen testing of infectious disease, and state‐of‐the‐art demos with innovative signal transduction mechanisms. Data‐driven strategies powered by machine learning are also reviewed, alongside integration into smart wearables for self‐adapting, responsive platforms. Finally, persisting challenges and present perspective of aerogel scaffolds in medicine research and practice are also discussed. Aerogel scaffolds are emerging as multifunctional biomedical platforms that bridge regenerative engineering and molecular diagnostics. By integrating hierarchical porosity, tunable mechanics, and programmable surface chemistry, aerogels can simultaneously support tissue reconstruction and enable localized biomarker sampling and signal transduction. Recent advances in sol–gel chemistry, freeze‐drying, electrospinning, and 3D printing have expanded structural precision from nanoscale to macroscale architectures, enabling tailored immunomodulation, neuroregeneration, sustained drug delivery, and bioactive wound management. Beyond structural support, aerogels increasingly function as intelligent interfaces for nucleic acid detection, pathogen sensing, and wearable bioelectronics through conductive networks and catalytic amplification mechanisms. The convergence of bioinspired design, composite engineering, and data‐driven analytics positions aerogel scaffolds as adaptive systems capable of coupling therapy with real‐time diagnostic feedback, advancing the development of next‐generation companion diagnostic biomaterials.