The tourism industry is a major economic sector worldwide, significantly contributing to job creation and GDP growth. However, the rapid expansion of this industry, along with rising environmental and social concerns, underscores the critical need for sustainable strategies. This paper presents a novel multi-objective game theory model that simultaneously optimizes profitability and sustainability in the tourism supply chain. The key innovation of this study lies in the integration of game theory with an artificial neural network (ANN) to predict customer demand, effectively capturing nonlinear consumer behaviors and enabling more accurate decision-making. The model analyzes the dynamic interactions between tour operators and local service providers, identifying Nash Equilibrium outcomes where no player can improve profitability through unilateral strategy adjustments. Additionally, the study introduces a comprehensive approach to government subsidies, evaluating their effectiveness in enhancing sustainability incentives and overall profitability. A detailed sensitivity analysis is conducted to examine how variations in pricing, sustainability efforts, and subsidy rates influence profit margins. Another distinctive contribution of this research is its emphasis on human resource management, highlighting how employee training, green organizational culture, and financial incentives can improve productivity and support sustainability initiatives. The results demonstrate that collaborative strategies, such as resource sharing and joint sustainability efforts between tour operators and local providers, significantly increase profitability. The findings further indicate that a combination of optimal pricing, maximum sustainability efforts, and full government subsidies yields the highest total profit of 6,395 units. Overall, this research offers strategic guidelines for pricing, human resource development, and subsidy policies, providing a robust framework for achieving both profitability and sustainability in the tourism supply chain.