AbstractThis article describes a bi‐level mixed‐integer quadratic problem on a healthcare network in which a defender protects clinics, hospitals, and medical centers concerning a given defensive budget for minimizing the transportation costs, and also the assignment of patients based on their initial capacity before and after interdiction operations. On the other hand, the attacker's subproblem involves the solution of an interdiction hierarchical problem with a total budget constraint on the disruption of the clinic, hospital, or medical center and the remaining capacity such that the total postattack costs are maximized. This problem is modeled as a bi‐level problem and the attacker and defender play a Stackelberg equilibrium strategy. An effective and fast hybrid approach of a genetic algorithm (GA), a simulated annealing (SA), and an exact algorithm was presented to solve the model. A realistic case study in the healthcare network is proposed to show the application of the new mathematical model and the effectiveness of the presented approach. The results are analyzed in comparison with GA and SA. Computational results indicate the superiority of hybrid algorithm against GA and SA based on accuracy and running time.