Spinal cord injury (SCI) results in many cellular dysfunctions that may cause severe and permanent neurological deficits. Given the intrinsically limited regenerative potential of the spinal cord and the complex inhibitory environment created by SCI, neural stem cell (NSC)-based therapy holds a great clinical potential. However, several pertinent obstacles hinder successful transplantation strategies. First, due to strong neuro-inflammation post-SCI, most NSCs die soon after transplantation. Second, the extracellular matrix at SCI sites is not very conducive to NSC survival and differentiation. To this end, we developed a multifunctional nanomaterial-based bioscaffold methodology: i) for the controlled delivery of therapeutic molecules; ii) to incorporate the bioscaffold into the enhanced transplantation of stem cell-derived neurons; and iii) to evaluate the combined therapeutic effect of spatiotemporal delivery of therapeutic molecules and stem cell therapy for the effective treatment of SCI using a rodent SCI model. Considering the difficulties of generating a robust population of functional neurons, enhancing neuronal behaviors (neurite outgrowth and axon regeneration), our biodegradable hybrid nanoscaffold can serve as a powerful tool for achieving an improved SCI treatment.