The area of drug delivery systems has witnessed significant advancements in recent years, with a particular focus on improving efficacy, stability, and patient compliance. Transdermal drug delivery offers numerous benefits compared to conventional methods of drug administration through the skin. It helps in avoiding gastric irritation, hepatic first-pass metabolism, and gastric degradation of the drug. It bypasses the gastrointestinal tract, eliminating the risk of first-pass metabolism and allowing drugs to be administered without being affected by pH, enzymes, or intestinal bacteria. Additionally, it allows for sustained release of the drug, is noninvasive, and enhances patient adherence to the treatment regimen. The transdermal drug delivery system (TDDS) can serve as an alternative route for drug administration in individuals who cannot tolerate oral medications, experience nausea, or are unconscious. When compared to intravenous, hypodermic, and other parenteral routes, TDDS stands out due to its ability to eliminate pain, reduce the risk of infection, and prevent disease transmission associated with needle reuse. Consequently, the overall patient compliance is significantly improved with the utilization of TDDS. Among the noteworthy developments are cubosomes and ethosomes, two distinct yet promising carriers that have garnered attention for their unique properties. In conclusion, this review synthesizes the current knowledge on cubosomes and ethosomes, shedding light on their individual strengths and potential synergies. The exploration of their application in various therapeutic areas underscores their versatility and establishes them as key players in the evolving landscape of drug delivery systems.