This study proposes several decision-making tools utilizing optimization and machine learning frameworks to assess and improve the safety of the workplaces. The first chapter of this study presents a novel mathematical model to optimally locate a set of detectors to minimize the expected number of casualties in a given threat area. The problem is formulated as a nonlinear binary integer programming model and then solved as a linearized branch-and-bound algorithm. Several sensitivity analyses illustrate the model's robustness and draw key managerial insights. One of the prevailing threats in the last decades, Active Shooting (AS) violence, poses a serious threat to public safety. The second chapter proposes an innovative mathematical model which captures several essential features (e.g., the capacity of the facility and individual choices, heterogeneity of individual behavioral and choice sets, restriction on choice sets depending on the location of the shooter and facility orientation, and many others) which are essential for appropriately characterizing and analyzing the response strategy for civilians under an AS exposed environment. We demonstrate the applicability of the proposed model by implementing the effectiveness of the RUN.HIDE.FIGHT.® (RHF) program in an academic environment. Given most of the past incidents took place in built environments (e.g., educational and commercial buildings), there is an urgent need to methodologically assess the safety of the buildings under an active shooter situation. Finally, the third chapter aims to bridge this knowledge gap by developing a learning technique that can be used to model the behavior of the shooter and the trapped civilians in an active shooter incident. Understanding how the civilians responded to different simulated environments, a number of actions could have been undertaken to bolster the safety measures of a given facility. Finally, this study provides a customized decision-making tool that adopts a tailored maximum entropy inverse reinforcement learning algorithm and utilizes safety measurement metrics, such as the percentage of civilians who can hide/exit in/from the system, to assess a workplace's safety under an active shooter incident.