This paper considers the application of scenario methods in multi-actor regional management to investigate and assess challenges in improving the effectiveness of managerial decision-making for sustainable and coordinated development under uncertainty and the impact of various destructive factors. The object of this study is an information and analytical support system for regional management. The aim of this study is to apply the scenario approach in order to form and justify a set of effectiveness assessment criteria for multi-actor regional management scenarios. The criteria are formed by analyzing the results of simulation modeling, encompassing both the event-level scenario descriptions and their closeness to given parameters of a target scenario. Using the mathematical apparatus of signed directed graphs, a comprehensive scenario-event simulation model of multi-actor regional management is developed. This model is intended to analyze and assess various management strategies with multiple actors, as well as to forecast the consequences of implementing these strategies. Based on the conducted research using the scenario-event model, scenarios of regional dynamics and their individual components are obtained. These scenarios are employed to identify key trends and factors influencing the stability and effectiveness of regional system management under growing external and internal threats. According to the scenario analysis results (the event-by-event encoding of event sequences and closeness to target parameters), the preferred management strategy based on the scenario analysis and situation forecasting in a rapidly changing environment is to shift the decision center to the state, possessing the greatest number of capabilities and influence mechanisms. This strategy shall be implemented on the principles of multi-actor management, relying on the coordination of actors to reduce the impact of external destructive effects from potential and existing adversaries and maintain socio-economic processes and stability in the region. When selecting a management strategy, one should keep in mind that incentive mechanisms for economic actors contribute to the prevention of conflicts and a uniform distribution of existing management capabilities and resources within the regional system.