Highly turbulent environment of dynamic job-shop operations affects shop-floor layout as well as manufacturing operations. Due to the dynamic nature of layout changes, essential requirements such as adaptability and responsiveness to the changes need to be considered in addition to the cost issues of material handling and machine relocation when reconfiguring a shop floor’s layout. Here, based on the source of uncertainty, the shop-floor layout problem is split into two sub-problems and dealt with by two modules: re-layout and find-route. Genetic algorithm is used where changes cause the entire shop re-layout, while function blocks are utilized to find the best sequence of robots for the new conditions within the existing layout. This chapter reports the latest development to the authors’ previous work.