Abstract: An important strategy to promote voluntary movements after motor system injury is to strengthen the connections between the motor cortex and muscles by taking advantage of the plasticity of the corticospinal motor system. Many neuromodulation approaches are directed to activate the spinal cord and peripheral axons to strengthen muscle activation. We discuss in this perspective that, the cortex and spinal cord should be targeted together to enhance cortex-to-muscle function (Amer and Martin, 2022). Among these protocols, we have used epidural intermittent theta burst stimulation (iTBS) of the motor cortex and transspinal direct current stimulation (tsDCS), a non-invasive approach targeting the cervical and rostral thoracic spinal cord (Song et al., 2016; Song and Martin, 2017; Amer et al., 2021; Amer and Martin, 2022; Williams et al., 2022). In a rodent model, we were the first to combine motor cortex iTBS and tsDCS, an approach that shows promise for clinical efficacy and translational potential for corticospinal tract lesion and spinal cord injury (SCI) (Song et al., 2016; Zareen et al., 2018; Figure 1). To move this, and other approaches, forward for translation it is important to understand the underlying mechanisms better. This will help guide the development of new synergistic strategies to boost the power of plasticity, and further, to guide plasticity for functional recovery after injury.