In this paper, a computational methodology combining the simulated annealing algorithm with two machine learning techniques to select a near-optimal safeguard set for business risk response is presented. First, a mathematical model with four types of risk factor responses (avoid, mitigate, transfer, and accept) is constructed. Then, the simulated annealing algorithm is applied to find a set of near-optimal solutions to the model. Next, these solutions are processed by the k-means clustering algorithm for identifying three categories, and with a decision tree classifier, the most relevant elements of each one are obtained. Finally, the categorized solutions are shown to the decision-makers through a user interface. These stages are designed with the aim of the users can take an appropriate safeguard set and develop one specific and optimal program to respond to business risk factors. The results generated by the proposed approach are reached in a reasonable time using less computational resources than those used by other procedures. Furthermore, the best results obtained by the simulated annealing algorithm use a lower business budget, and they have a relative-error less than 0.0013% of the optimal solution given by a deterministic method.