Background <p>Clinical learning is the cornerstone of nursing education, integrating theoretical knowledge with hands-on practice to develop essential clinical skills, critical thinking, and professional confidence. Nursing students’ face major challenges, including a shortage of qualified clinical instructors, overcrowded clinical sites, and limited clinical equipment, which hinder their skill development and clinical competence at Wolaita Sodo University, South Ethiopia. Despite its importance, evidence on the extent and determinants of these challenges in the study area is limited.</p> Objective <p>This study aimed to assess the prevalence and determinants of clinical learning challenges among nursing students at Wolaita Sodo University, South Ethiopia.</p> Methods <p>A cross-sectional study was conducted from May 15 to June 2024 among 303 nursing students at Wolaita Sodo University using structured self-administered questionnaires. Participants were selected using a stratified random sampling technique. Data were analyzed using SPSS version 26. Descriptive statistics summarized the data, while logistic regression identified factors associated with clinical learning challenges. Anxiety and depression were measured using validated tools (GAD-7 and PHQ-9), while khat use was assessed with a self-report questionnaire adapted from previous Ethiopian university studies. The questionnaire demonstrated good reliability, with the following domain-specific Cronbach’s alpha values: clinical learning challenges (α = 0.81), skill lab and supervision experience (α = 0.78), financial and emotional stressors (α = 0.80), and coping mechanisms (α = 0.76).</p> Results <p>Out of 303 students, 293 responded completely the questionnaire (response rate: 96.7%). Among them, 232 (79.2%) reported facing one or more clinical learning challenges. Major challenges included lack of clinical instructors (64.6%), overcrowding at clinical sites (58.4%), and inadequate learning resources (52.8%). Factors significantly associated with challenges were Overcrowding in clinical areas (AOR = 1.88,95% CI: 1.12–3.16, <i>p</i> = 0.017), Khat chewing (AOR = 2.33, 95% CI: 1.20–4.51, <i>p</i> = 0.011), Inadequate clinical materials and equipment (AOR = 1.76, 95% CI: 1.01–3.05, <i>p</i> = 0.045), Moderate anxiety (AOR = 2.87, 95% CI: 1.14–7.18, <i>p</i> = 0.001), First- and second-year (AOR = 1.59 ,95% CI: 1.04–2.42, <i>p</i> = 0.031).</p> Conclusion <p>This study revealed a high prevalence of clinical learning challenges among nursing students at Wolaita Sodo University, mainly linked to year of study, instructor availability, and student–patient ratio. Addressing these issues through stronger instructor support, equitable clinical access, and balanced student loads is essential. The findings highlight the need for institutional reforms to enhance clinical education quality and student competency. Institutions should also manage faculty workload, provide targeted training, and align the national nursing curriculum with real-world clinical demands.</p> Clinical trial number <p>Not applicable.</p>