Background <p>Nurses are pivotal in in-hospital cardiac arrest response, yet their initiation of resuscitation (IOR) decisions are complex. Limited data exists on factors impacting critical care nurses’ IOR decisions, particularly in Iran. Therefore, this qualitative study aims to explore the multifaceted factors shape Iranian critical care nurses’ IOR decision-making.</p> Methods <p>This qualitative descriptive study used conventional content analysis to explore factors influencing Iranian critical care nurses’ IOR decision-making. Sixteen nurses from three university hospitals were sampled purposefully. Semi-structured interviews were conducted until data saturation. Data analysis followed Graneheim and Lundman’s approach, ensuring rigor through Lincoln and Guba’s criteria. The study adhered to ethical standards and the COREQ checklist for transparent reporting.</p> Findings <p>The analysis revealed three overarching themes influencing Iranian critical care nurses’ IOR decision-making: personal, relational, and systemic factors. Personal factors included individual perceptions and capacities (mental frameworks, personality, competence, normalization of death, and post-resuscitation concerns). Relational dynamics highlighted interprofessional, intraprofessional, and nurse-patient-family dynamics. Systemic influences encompassed organizational culture, lack of formal policies, management issues, and organizational support.</p> Conclusion <p>Individual beliefs, interpersonal dynamics, and systemic constraints collectively shape Iranian critical care nurses’ initiation of resuscitation decisions, underscoring the need for targeted education, policy development, and organizational support.</p> Implications for clinical practice <p>Improving critical care nurses’ IOR decisions requires targeted education, fostering interprofessional collaboration, enhancing organizational support, and developing clear policies to address personal, relational, and systemic challenges.</p> Trial registration <p>Not applicable.</p>