Disclosed herein are embodiments of systems, methods, and products comprise an analytic server, which detects and defends against malware in-flight regardless of the specific nature and methodology of the underlying attack. The analytic server learns the system's normal behavior during testing and evaluation phase and trains a machine-learning model based on the normal behavior. The analytic server monitors the system behavior during runtime comprising the runtime behavior of each sub-system of the system. The analytic server executes the machine-learning model and compares the system runtime behavior with the normal behavior to identify anomalous behavior. The analytic server executes one or more mitigation instructions to mitigate malware. Based on multiple available options for mitigating malware, the analytic server makes an intelligent decision and takes the least impactful action that have the least impact on the system to maintain mission assurance.