Background: Timely pain management in emergency departments (EDs) is critical to improve patient outcomes. Nurse-initiated protocols (NIPs) allow nursing staff to administer treatment, analgesia and corticosteroids without waiting for physician orders, reducing treatment delays and enhancing care quality. We aimed to evaluate the clinical effectiveness and implementation challenges of nurse-initiated protocols for pain management and corticosteroid administration in EDs. Methods: A systematic review was conducted in accordance with PRISMA guidelines. Databases searched included PubMed, Scopus, CINAHL, and ScienceDirect. Eligible studies assessed nurse-initiated interventions for analgesia or corticosteroids in ED settings and reported on clinical or process outcomes. Data were synthesized qualitatively and categorized by intervention type and outcomes. Results: Seven studies met inclusion criteria, including pediatric and adult populations with asthma, trauma, and musculoskeletal pain. Nurse initiated protocols reduced time to medication delivery, improved pain control, increased protocol adherence, and enhanced patient satisfaction. For pediatric asthma, early corticosteroid administration led to reduced admission rates and faster recovery. Barriers to implementation included limited staff confidence, time constraints, and inadequate training, and enablers included protocol standardization andstrong nursing autonomy. Conclusion: Nurse-initiated protocols in EDs are effective in improving the timeliness and quality of pain and asthma management. Widespread adoption optimize patient outcomes, though challenges in implementation require attention.