Predictive models were developed to assess the growth response of Clostridium sporogenes in “requeijão cremoso” processed cheese, as affected by pH and sodium chloride and nisin concentrations. A complete factorial design was performed using different formulations: pH (5.2, 5.6, and 6.0), sodium chloride (0.5, 0.75, 1.0, 1.25, and 1.5%), and nisin (0.0, 5.0, 7.5, 10.0 and 12.5 mg/kg), totalizing 75 conditions. Packs with 150 g of “requeijão cremoso” were inoculated with 103 spores/g following storage at 10 °C for up to 60 days. The counts of C. sporogenes were performed on day zero and at the end of storage after a heat shock (80 °C for 12 min). The formulations that allowed an increase in the population >1 log CFU/g were assigned the value of 1 (growth), and the formulations in which the increase was <l log CFU/g were assigned 0 (no growth). Overall, the growth of C. sporogenes was affected by pH, salt concentration and nisin, e.g. at pH 5.2 the growth/no growth limit is 1.25% salt and no nisin, at pH 5.6 this limit is reduced to 0.75% salt, while at pH 6.0 only the effect of pH was sufficient to inhibit C. sporogenes even in the absence of salt and nisin. All isolated parameters and their combinations significantly affected spore germination, indicating that the model generated significantly contributes to the optimization of the processing and mitigation of the microbiological spoilage of “requeijão cremoso” processed cheese by Clostridia.