The advanced nurse practitioner (ANP) role first developed in the USA in the 1960s in primary care. Since then, it has evolved in many different countries and subspecialties, creating a variety of challenges for those designing and implementing master’s programs for this valuable professional group. We focus on ANPs in the neonatal and pediatric intensive care setting to illustrate the complexity of issues faced by both faculty and students in such a program. We review the impact of limited resources, faculty recruitment/accreditation, and the relationship with the medical profession in establishing a curriculum. We explore the evidence for the importance of ANP role definition, supervision, and identity among other health professionals to secure a successful role transition. We describe how recent advances in technology can be used to innovate with new styles of teaching and learning to overcome some of the difficulties in running master’s programs for small subspecialties. We illustrate, through our own experience, how a thorough assessment of the available literature can be used to innovate and develop strategies to create an individual MSc programs that are designed to meet the needs of highly specialized advanced neonatal and pediatric nursing practice.