In the last few years, single cell and single nucleus RNA-sequencing technologies have been leveraged in exercised adult skeletal muscle to reveal complex cell type-specific regulation of muscle plasticity. Expanding -omics technology at single cell resolution, complimented by advanced computational approaches, promise to rapidly accelerate our understanding of how exercise confers its numerous beneficial effects, paving the way for cell type-specific and targeted therapeutics to increase exercise responses during aging and in the face of chronic disease.