Abstract Purpose Unexpected events, whether man-made or natural, cause significant distress and disorder. The number and magnitude of disasters and catastrophes have been rising globally in recent decades, according to historical data. Continued real-time monitoring of mass casualty along with the arrangement of needed medical resources to handle the mass casualty is required to reduce the mortality and morbidity rates. Methods Electronic tag-based casualty monitoring and machine learning-based Decision Support Systems are emerging as a more effective and proactive solution that provides continuous remote monitoring of patients. A novel framework based on Body-to-Body Network, Prediction model, and Genetic Algorithm-based medical resource optimization is proposed for the continuous monitoring of the mass casualty and medical resource allocation at the incident. The aim of this work is to give priority to the handling of critical casualties. Firstly, a Quality of Service and load-sensitive routing protocol for transmitting mass casualties' physiological parameters across a wireless network is proposed, with the critical casualty being emphasized. Secondly, the clinical seriousness degree of the mass casualty is predicted using Backpropagation Artificial Neural Network. Finally, an optimization model using a Genetic algorithm and queuing theory is proposed to find the required optimal number of medical resources to handle critical and non-critical casualties separately. Also, the proposed optimization model considers the predicted clinical level transition rates of the mass casualty. Results The performance and accuracy of the proposed framework are evaluated using the MIMIC-II dataset. The outcome demonstrates that the framework emphasizes critical casualty management. Furthermore, the framework allocates an adequate number of servers by incorporating the proposed routing protocol in comparison to the AODV protocol. Conclusion The inclusion of a prediction model in the framework aids in allocating an adequate number of servers by considering the predicted clinical deteriorating transition rates of casualties at a mass casualty incident. In terms of the estimated length of the casualty at the incident, the results suggest that incorporating a medical resource optimization model outperforms the non-optimal option.