mRNA-based therapies have shown clear evidence of their potential to treat many diseases, thanks to the development of Lipid Nanoparticles (LNPs), which effectively deliver mRNA inside the target cells. In addition to LNPs, other strategies have been followed to try to safely deliver mRNA in vivo. Our technology, based on vitamin E (VE) and sphingomyelin (SM) nanoemulsions (NEs) have previously shown potential to deliver macromolecules in vitro and in vivo, such as peptides, proteins and aptamers. In this work, we explored the potential of our NEs for effective in vivo mRNA delivery. Using FLuc mRNA as a reporter gene, we optimized our technology and obtained four final prototypes with distinguished ratios of VE and SM, all of them with good colloidal properties, stability and with encapsulation efficiencies above 90%. We then studied their in vitro and in vivo performance, resulting in high transfection efficiencies and distinguished biodistribution patterns depending on the composition tuning. VE-enriched NEs showed preferential hepatic delivery, making them a great candidate for protein replacement therapies or gene editing approaches targeting the liver. Likewise, SM-enriched NEs showed protein production shift towards spleen, indicating that these are good candidates for immuno-onocology or vaccine applications.