This meeting will highlight fundamental and clinical research investigating how individuals in early life form protective defenses while avoiding harmful inflammatory or autoimmune reactions, directly informing vaccine design, allergy prevention, and strategies to reduce neonatal and pediatric infection mortality. The goals of the meeting include: 1) generate new scientific knowledge by discussing the mechanisms of early life immune development and host defenses and how these function under homeostatic and disease states with a balance of fundamental and clinical talks; 2) Foster collaboration, training and cross-disciplinary exchange by building a cohesive community across immunology, microbiology, clinical pediatrics. By challenging the notion of early immunity as merely “immature,” the program reframes tolerance and defense as dynamic, age specific processes. By consolidating methodological advances with paradigm shifting science and fostering a deeply collaborative ethos, this meeting will propel the field beyond descriptive studies of infant immune “deficits.” Instead, it will catalyze a proactive, systems level understanding of how tolerance and defense are orchestrated in early life. Ultimately, this will accelerate the development of age tailored vaccines, microbiome-based therapeutics, and precision medicine approaches that safeguard health from birth—and lay the groundwork for lifelong immune resilience.