Given the non-repeatability, complexity, and unpredictability of unconventional public health emergencies, building accurate models and making effective response decisions based only on traditional prediction–response decision-making methods are difficult. To solve this problem, under the scenario–response paradigm and theories on parallel emergency management and discrete event system (DES), the parallel simulation decision-making framework (PSDF), which includes the methods of abstract modeling, simulation operation, decision-making optimization, and parallel control, is proposed for unconventional public health emergency response processes. Furthermore, with the example of the severe acute respiratory syndrome (SARS) response process, the evolutionary scenarios that include infected patients and diagnostic processes are transformed into simulation processes. Then, the validity and operability of the DES–PSDF method proposed in this paper are verified by the results of a simulation experiment. The results demonstrated that, in the case of insufficient prior knowledge, effective parallel simulation models can be constructed and improved dynamically by multi-stage parallel controlling. Public health system bottlenecks and relevant effective response solutions can also be obtained by iterative simulation and optimizing decisions. To meet the urgent requirements of emergency response, the DES–PSDF method introduces a new response decision-making concept for unconventional public health emergencies.