Historically, the lack of consensus and wide variability in defining RIF—combined with its multifactorial etiologies—created significant diagnostic and therapeutic hurdles for both patients and clinicians. While recent international frameworks have helped establish clearer diagnostic criteria and a deeper understanding of endometrial–embryo interactions, managing true RIF remains complex. In this 2027 course, we will review the current state of evidence-based diagnostics, critically evaluate emerging biomarkers and AI-driven embryo/endometrial assessments, and explore the most promising, clinically validated therapeutic strategies for patients facing RIF.