Organophosphorus nerve agents, such as VX, pose an extreme risk due to their high dermal toxicity, environmental persistence, and rapid systemic absorption. Timely and effective decontamination is crucial for reducing exposure and minimizing health effects. This study outlines a two-phase approach to develop and validate a new surfactant-based decontamination solution, beginning with simulant testing using phorate and progressing to efficacy trials with real VX. In phase one, phorate was used as a simulant for VX in dermal exposure studies. Two prototype detergents (F1 and F2) were tested on full-thickness porcine skin using static Franz-type diffusion cells. A ¹⁴C-labelled phorate droplet was applied, followed by no treatment, water-only rinse, or detergent application using the ORCHIDS microfibre protocol. Absorption was measured via liquid scintillation counting. Phase two involved testing an optimized formulation (Formula 3), informed by the results of Phase one, against ¹⁴C-labelled VX on full-thickness human abdominal skin. Decontamination occurred 60 minutes post-application, comparing water-only and detergent treatment. Autoradiography and scintillation counting were used to quantify residual agent. In the simulant phase, both detergents significantly reduced phorate absorption compared to water or no treatment, with Formula 2 performing best by limiting wash-in effects. Subsequent VX testing showed Formula 3 significantly reduced residual agent on the skin surface compared to water alone, indicating effective decontamination under realistic exposure conditions. This two-stage research strategy demonstrates that simulant screening is a valuable tool for optimizing decontamination solutions. The final detergent formulation provides an effective countermeasure for dermal exposure to VX, with potential applications in defense and civilian emergency response.