Gold nanoparticles have been synthesized inside ethosomes, vesicles composed of phospholipid, ethanol and water, which could be very efficient not only in delivery probes to the skin but also as diagnostic and therapeutic multimodal agents. High efficiency encapsulation of gold nanoparticles is achieved by a simple strategy: the nanoparticles synthesis occurs simultaneously with the ethosomes formation, in the absence of any undesirable reducing agents. A three-dimensional reconstruction of a gold-embedded ethosome generated by cryoelectron tomography reveals that the gold particle is localized inside the lipid bilayer, leaving the ethosome surface and core free for further functionalization. The resulting gold nanoparticles are homogeneous in size and shape and, depending on synthesis temperature, the size ranges from 10 to 20 nm, as revealed by TEM. The ethosome-nanoparticles hybrids size has been investigated by means of dynamic light scattering and has been found to vary with temperature and gold salt concentration from 700 to 400 nm. Gold nanoparticles encapsulated ethosomes offer a versatile platform for the enhancement of pharmacological efficacy in transdermal and dermal delivery systems. ; Comment: 2 videos of the cryo-electron tomographic reconstruction in Supporting Information