Firm survival, as a key indicator of regional economic resilience, has gained increasing attention in the context of global economic uncertainty and the deep adjustments in industrial structures. In the Pearl River Delta (PRD), a core region of China’s Guangdong-Hong Kong-Macau Greater Bay Area, the characteristics of firm life cycles are crucial for understanding spatial development inequalities and institutional effects in emerging economies. This study focuses on firms in the PRD, using full life-cycle data from registration, operation, to deregistration. An XGBoost regression model is employed, incorporating the SHAP explanation algorithm, to systematically analyze the main factors influencing firm survival. The results show that: (1) Firm establishment time is the primary factor influencing survival, with significant “survival threshold” and “growth leap” effects—mature firms exhibit a distinct survival advantage; (2) Among spatial structure variables, moderate industry specialization and diversity enhance firm survival rates, while excessive concentration and diversification show diminishing or negative returns, reflecting an “ecological threshold” effect; (3) External shocks have a significant suppressive impact on startups, while policy support and capital size show limited explanatory power; (4) The ownership structure, especially state-holding, has a positive moderating effect on firm survival in specific contexts, indicating that private enterprises’ flexibility and adaptability can compensate for institutional gaps. This study offers insights into the spatial heterogeneity of firm survival mechanisms, providing quantitative evidence for regional economic policy adjustments and firm resilience-building. Recommendations include promoting differentiated policies, optimizing industrial ecological spatial layouts, and piloting systems to enhance survival resilience, especially for mixed-ownership firms.