This work examined the mineralization of unsymmetrical dimethylhydrazine (UDMH) as an alarming organic contaminant, via persulfate (PS) oxidation process. Nano zero-valent iron (NZVI) particles, as a source of ferrous ions, were synthesized and used to activate PS ions in the media. The effective operational parameters such as NZVI dosage, pH, and initial amount of PS were optimized by response surface methodology as a statistical experimental design. The mineralization efficiency and the demand-operating cost (DOC) of the process were well modeled by two second-order polynomial equations. Based on the desirability, function optimization of the responses was performed. In the optimum condition of pH 3.45, [PS]0 = 836.16 mg L−1, and [NZVI]0 = 158.45 mg L−1, the model predicted 91% of the UDMH mineralization and 10 US$/m3 for the DOC that the electrical energy constitutes 69% of the total cost. Compared with the related literatures about treatment of the UDMH, the applied NZVI/PS process reached a high efficiency using lower chemicals.