Traumatic injury to the spinal cord (SCI) and brain (TBI) are serious health problems and affect many people every year throughout the world. These devastating injuries are affecting not only patients but also their families socially as well as financially. SCI and TBI lead to neurological dysfunction besides continuous inflammation, ischemia, and necrosis followed by progressive neurodegeneration. There are well-established changes in several other processes such as gene expression as well as protein levels that are the important key factors to control the progression of these diseases. We are not yet able to collect enough knowledge on the underlying mechanisms leading to the altered gene expression profiles and protein levels in SCI and TBI. Cell loss is hastened by the induction or imbalance of pro- or anti-inflammatory expression profiles and transcription factors for cell survival after or during trauma. There is a sequence of events of dysregulation of these factors from early to late stages of trauma that opens a therapeutic window for new interventions to prevent/restrict the progression of these diseases. There has been increasing interest in the modulation of these factors for improving the patient’s quality of life by targeting both SCI and TBI. Here, we review some of the recent transcriptional factors and protein biomarkers that have been developed and discovered in the last decade in the context of targeted therapeutics for SCI and TBI patients.