: Microemulsions (MEs) are considered for preparing drug delivery carriers, especially transdermal vehicles. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage chronic and acute pain and inflammatory diseases. However, NSAIDs have drawbacks such as gastrointestinal tract disorders and poor pharmacokinetic properties for oral administration. To address these issues, we evaluated the potential of ME as a transdermal system for locally delivering naproxen (NPX) as an NSAIDs model (NPX-MEs). Phase diagrams were constructed for MEs composed of tween 80, span 80, and propylene glycol (PG) as surfactant (S)/cosurfactant (CS), transcutol® P (TRC-P), and LabrafacTM PG as oil. The final concentration of NPX in MEs was 1% (w/v). The MEs were analyzed for particle size, refractive index, and viscosity. In vitro permeability studies of NPX-MEs were conducted using Franz diffusion cells on rat skin samples. Additionally, the effects of Eucalyptus oil (EU oil), oleic acid (OLA), and TRC-P as enhancers on the skin permeation of NPX were investigated. The particle size and viscosity values of the NPX-MEs ranged from 7.05 ± 0.03 to 79.56 ± 0.58 nm and 222.4 ± 0.87 to 681.13 ± 1.97, respectively. The optimal formulation, ME-3, consisted of 20% oil, 10% water, and 70% S/C phases. The skin permeation rates of NPX from ME-3 were higher than those of other formulations (Dapp = 1.36 ± 0.616, ERD=527.989 ± 313.627) with a lower lag time. Additionally, OLA-treated skin showed the highest transdermal permeation rate (ERD = 75.55 ± 23.532). Based on these results, the formulated NPX-ME may be a desirable carrier for transdermal delivery compared to traditional formulations, potentially reducing side effects and improving the therapeutic efficacy of NPX.