Background: Early definitive fixation improves pulmonary outcomes and mobilization in polytrauma. In traumatic brain injury (TBI), timing remains contested due to risks of secondary brain insults. Translational data suggest that parenchymal TBI releases neuron?derived small extracellular vesicles (sEVs) enriched with miR?21?5p and triggers systemic inflammatory/neuropeptidergic responses, potentially accelerating callus formation while increasing neurogenic heterotopic ossification (NHO) risk. Case: A 58?year?old man sustained severe TBI (Glasgow Coma Scale 6) with a Pipkin IV femoral head fracture (ISS 22). Neurocritical care lowered intracranial pressure medically; no decompressive craniotomy was performed. After physiological stabilization, the hip injury underwent open reduction and internal fixation via an anterolateral (Watson–Jones) approach. The case is framed across the emergency department–intensive care unit (ER–ICU) continuum with a physiology?gated algorithm. Discussion: Evidence supports early definitive fixation once resuscitation targets are met. A neuron?derived sEV/miR?21–inflammation axis provides a mechanistic rationale for expedited osteogenesis after TBI, while underscoring proactive NHO surveillance/prophylaxis. Conclusion: A physiology?gated strategy reconciles neuroprotection with early fixation after TBI; the present case illustrates feasibility without craniotomy, consistent with vesicle? and cytokine?mediated systemic effects.