The computational approach to designing vaccines has several useful characteristics over traditional vaccine development, such as being highly specific, less time-consuming and less expensive. Thus, this chapter describes an immunoinformatics workflow to design a vaccine against a member of the Poxviridae family known as Monkeypox virus. The immunoinformatics approach uses several online servers to select highly antigenic and non-allergenic CTL, HTL, and B cell epitopes. Then, it links the predicted epitopes through linkers and submit them for 3D structure modeling. Afterward, the modeled vaccine is docked with TLRs to check the induction of the immune system. Finally, immune simulations are performed to check the level of several immune factors like IgG, IgM, cytokines and interleukins, among others, upon the injection of the constructed vaccine. This approach can be used to successfully design novel and effective vaccine candidates against emerging species from the Poxviridae family.