The microbiological, biochemical, and physicochemical changes of ready-to-eat shrimps (Penaeus vannamei) with high water content, subjected to nisin treatment in combination of hurdle technology, were investigated. The ready-to-eat shrimps were processed by boiling, drying, treatment with nisin solution, seasoning, and roasting, followed by vacuum packaging, sterilization, and storage at room temperature (25°C). The results showed that the samples treated with nisin in combination with other hurdles resulted in a significant decrease in bacterial counts (Bacillus cereus and native microflora) compared to the control samples. Additionally, the nisin-treated samples possessed better biochemical and physicochemical properties, as well as better sensory patterns. According to the safety guidelines for roasted shrimp (SC/T 3305-2003), the shelf life of ready-to-eat shrimp with 48–53% moisture content was extended by nisin application at concentrations of 60 and 100 mg/kg of nisin; specifically, ready-to-eat shrimp maintained good quality from 4–6 days up to 6–12 and 8–14 days corresponding to 60 and 100 mg/kg of nisin treatments, respectively. Nisin treatment combined with hurdle technology in the production of ready-to-eat shrimp provides a highly valued product in China.