Traumatic brain and spinal cord injuries cause permanent disability. Although progress has been made in understanding the cellular and molecular mechanisms underlying the pathophysiological changes that affect both structure and function after injury to the brain or spinal cord, there are currently no cures for either condition. This may change with the development and application of multi-layer omics, new sophisticated bioinformatics tools, and cutting-edge imaging techniques. Already, these technical advances, when combined, are revealing an unprecedented number of novel cellular and molecular targets that could be manipulated alone or in combination to repair the injured central nervous system with precision. In this review, we highlight recent advances in applying these new technologies to the study of axon regeneration and rebuilding of injured neural circuitry. We then discuss the challenges ahead to translate results produced by these technologies into clinical application to help improve the lives of individuals who have a brain or spinal cord injury.