Background: Emergency Medical Services (EMS) response times are critical for optimizing patient outcomes, particularly in time-sensitive emergencies. This study explores the multifaceted determinants of EMS response times, leveraging machine learning (ML) techniques to identify key factors such as urgency levels, environmental conditions, and geographic variables. The findings aim to inform strategies for enhancing resource allocation and operational efficiency in EMS systems. Methods: A retrospective analysis was conducted using over one million EMS missions from Stockholm, Sweden, between 2017 and 2022. Advanced ML techniques, including Gradient Boosting models, were applied to evaluate the influence of diverse variables such as call handling times, travel times, weather patterns, and resource availability. Feature engineering was employed to extract meaningful insights, and statistical models were used to validate the relationships between key predictors and response times. Results: The study revealed a complex interplay of factors influencing EMS response times, aligning with the study’s aim to deepen the understanding of these determinants. Key drivers of response time variability included weather conditions, call priority, and resource constraints. ML models, particularly Gradient Boosting, proved effective in quantifying these impacts and provided robust predictions of response times across scenarios. By providing a comprehensive evaluation of these influences, the results support the development of adaptive resource allocation models and evidence-based policies aimed at enhancing EMS efficiency and equity across all call priorities. Conclusions: This study underscores the potential of ML-driven insights to revolutionize EMS resource allocation strategies. By integrating real-time data on weather, call types, and workload, EMS systems can transition to adaptive deployment models, reducing response times and enhancing equity across priority levels. The research provides a blueprint for implementing predictive analytics in EMS operations, paving the way for evidence-based policies that improve emergency care efficiency and outcomes. Clinical trial number: Not applicable.