Taking data collected at point of care, analyzing, and determining actionable insights in order to drive decision making is the pinnacle of a learning healthcare system. The rise of “big data” and focus on artificial intelligence leads to healthcare data becoming more abundant, diverse, useful, and able to impact healthcare decisions in real time. Data-driven approaches based on the analysis of clinical databases linked to data collected at the individual level provide unique opportunities to evaluate variations in clinical practice and the impact of treatment and diagnostic decisions on patient outcomes. Measuring outcomes in meaningful ways, along with the ability to analyze and communicate actionable trends within and across healthcare stakeholders and settings, brings wide-ranging opportunities for health economics and outcomes research (HEOR) to become a relevant part of clinical decision making. Join this exciting exploration of the collaborative approaches to clinical decision making and ways that HEOR could strengthen health service delivery and enhance the patient experience.