Many preclinical studies seek cures for spinal cord injury (SCI), but when the results are translated to clinical trials they give scant efficacy. One possible reason is that most strategies use treatments directed toward a single pathological mechanism, while a multitherapeutic approach needs to be tested to significantly improve outcomes after SCI. Most of the preclinical reports gave better outcomes when a combination of different compounds was used instead of a single drug. This promising approach, however, must still be improved because it raises some criticism: (i) the blood-spinal cord barrier limits drug distribution, (ii) it is hard to understand the interactions among the pharmacological components after systemic administration, and (iii) the timing of treatments is crucial: the spread of the lesion is a process finely regulated over time, so therapies must be scheduled at precise times during the postinjury course. Nanomedicine could be useful to overcome these limitations. Nanotools allow finely regulated drug administration in terms of cell selectivity and release kinetics. We believe that excellent therapeutic results could be obtained by exploiting this tool in multitherapy. Combining nanoparticles loaded with different compounds that act on the main pathological pathways could overcome the restrictions of traditional drug delivery routes, a major limit for the clinical application of multitherapy. This review digs into these topics, discussing the critical aspects of multitherapies now proposed and suggesting new points of view.