The present study focused on the formulation and characterization of Isoconazole-loaded invasomal gel employing a Box-Behnken design. Isoconazole invasomes were synthesized using the conventional thin-layer evaporation method. For optimization, a 2-level 3 factor factorial design was executed using Design of Expert 12 software (DOE 12 trial version). The optimization involved a Response Surface Quadratic model, and 17 experimental runs were designed. The resulting formulations were systematically characterized with a focus on drug entrapment efficiency and particle size. The evaluation of the prepared Invasomes formulations included key parameters such as vesicle size, polydispersity index (PDI), and entrapment efficiency. These parameters are crucial for determining the stability, uniformity, and efficacy of the formulated Isoconazole-loaded Invasomal gel. The obtained results provide insights into the effectiveness of the developed formulations, paving the way for potential applications in dermatological drug delivery systems.