Background and Objectives: Working in pediatric and neonatal intensive care units (ICUs) can be challenging and differs from work in adult ICUs. This study investigated for the first time the perceptions, experiences and challenges that healthcare professionals face when dealing with end-of-life decisions in neonatal intensive care units (NICUs) and pediatric intensive care units (PICUs) in Croatia. Materials and Methods: This qualitative study with focus groups was conducted among physicians and nurses working in NICUs and PICUs in five healthcare institutions (three pediatric intensive care units (PICUs) and five neonatal intensive care units (NICUs)) at the tertiary level of healthcare in the Republic of Croatia, in Zagreb, Rijeka and Split. A total of 20 physicians and 21 nurses participated in eight focus groups. The questions concerned everyday practices in end-of-life decision-making and their connection with interpersonal relationships between physicians, nurses, patients and their families. The constant comparative analysis method was used in the analysis of the data. Results: The analysis revealed two main themes that were the same among the professional groups as well as in both NICU and PICU units. The theme “critical illness” consisted of the following subthemes: the child, the family, myself and other professionals. The theme “end-of-life procedures” consisted of the following subthemes: breaking point, decision-making, end-of-life procedures, “spill-over” and the four walls of the ICU. The perceptions and experiences of end-of-life issues among nurses and physicians working in NICUs and PICUs share multiple common characteristics. The high variability in end-of-life procedures applied and various difficulties experienced during shared decision-making processes were observed. Conclusions: There is a need for further research in order to develop clinical and professional guidelines that will inform end-of-life decision-making, including the specific perspectives of everyone involved, and the need to influence policymakers.