<p>Despite advancements in mechanical fixation, impaired fracture healing remains a significant clinical challenge, largely driven by immunometabolic dysregulation within the bone marrow niche. Conditions such as prolonged M1 macrophage activation, disrupted metabolic homeostasis, and mitochondrial dysfunction collectively stall the regenerative cascade and push skeletal progenitors toward senescence or adipogenesis. This review comprehensively explores the paradigm shift from purely mechanical stabilization to immunometabolic reprogramming using bioactive materials to rescue impaired bone repair. We systematically categorize biomaterial-driven interventions into three core pillars: metal ion-releasing systems that orchestrate immune-osteogenic crosstalk, metabolism-targeted delivery platforms that suppress aerobic glycolysis to alleviate inflammatory stress, and mitochondria-protective strategies that scavenge reactive oxygen species to restore cellular bioenergetics. Furthermore, we emphasize the critical importance of spatiotemporal design—such as phase-matched degradation kinetics, sequential drug release, and localized deployment—to synchronize material function with physiological healing stages while minimizing ectopic ossification. Ultimately, integrating these advanced biomaterial strategies with emerging diagnostic tools, such as single-cell profiling, offers a promising framework for personalized, precision-guided therapies to overcome complex bone regeneration failures in compromised clinical scenarios.</p> Graphical Abstract <p></p>