Background: Insufficient experience and practical knowledge makes challenges in addressing health-care practice-related issues. Being a professional nurse after completing your nursing studies is a challenging time. Most frequently, the quantity of patients with severe illnesses and co-morbidities, the lack of mentorship, performance anxiety, communication issues, and the blame/complaint culture are blamed for the difficulties faced by inexperienced nurses. The study aimed to identify the challenges and the associated factors which limit the knowledge acquisition of new nurse graduates in Oman. Methodology: Using a cross-sectional study design, 104 people were selected as a sample from Ibri Hospital. We have adopted convenience and snowball sampling methods to reach out to the participants. The data was collected between June, 2022, to September, 2022. Data from nurses was gathered by a primary survey approach utilizing a closed-ended questionnaire. The statistical analysis was carried out using IBM SPSS (Statistical Tool for Social Sciences) version 20.0. Results: Nursing professionals face a number of obstacles, including role expectations, lack of confidence, workload, fear, and orientation concerns. In addition, variables including the physical environment, responsibility, support, and professional development contribute to their dissatisfaction. It is rare for newly graduated nurses to be assigned to cases where they lack the confidence to handle clinical cases. The study also found positive relationship between preceptor support and leadership/communication, organizing and prioritizing, professional satisfaction, and work satisfaction. Conclusion: The study came to the conclusion that the main problem facing nurses in the healthcare setting is transition. During their transitional time, newly graduated nurses face a variety of obstacles related to job expectations, confidence, workload, orientation, and concerns. To overcome these obstacles, nursing administrators and preceptors must come up with and apply important solutions. As a result, the current study suggests that transitional support initiatives are helpful in assisting recently graduated nurses. Also, hospital orientation programs are necessary to adapt to the changing demands of new nurses in a constantly evolving healthcare setting.