Background: Despite growing attention to ICU quality care, limited evidence has simultaneously examined the combined influence of nursing culture and clinical competence on compliance with standardized pain-sedation assessment among ICU nurses in developing healthcare settings. This study aimed to identify factors associated with ICU nurses’ compliance with standardized pain and sedation assessment using the COMFORT Scale and the Richmond Agitation-Sedation Scale (RASS), with a particular focus on the combined roles of nursing culture and clinical competence. Methods: A quantitative descriptive survey design was employed. This cross-sectional study was conducted and reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. The study included 35 ICU nurses at a tertiary hospital in South Kalimantan, Indonesia, using a total population sampling method. All ICU nurses who met the inclusion criteria were eligible to participate. The dependent variable was ICU nurses' compliance with standardized pain and sedation assessment, measured using structured observation checklists based on the COMFORT Scale and the Richmond Agitation-Sedation Scale (RASS). The independent variables were nursing culture and clinical competence, measured using validated questionnaires. Observers were trained and standardized before data collection to ensure consistency of assessment. Data were analyzed using descriptive statistics, Spearman's rho correlation, and multiple linear regression after assessing model assumptions, including linearity, multicollinearity, normality of residuals, and homoscedasticity. Statistical significance was set at p < 0.05. Results: Most participants were female nurses (65.7%) aged 30–39 years (51.4%) with ≤5 years of ICU experience (62.9%). Observed compliance with standardized pain and sedation assessment was moderate and inconsistent (Mean = 3.59 ± 0.505 on a 1–5 scale), with documentation and scheduled tracking intervals being the weakest domains. Bivariate analysis revealed that both a supportive nursing culture (r = -0.001, p = 0.002) and higher clinical competence (r = 0.912, p < 0.001) were significantly correlated with compliance. However, in the multiple linear regression model (R2 = 0.574, F(2,32) = 21.562, p < 0.001). Individual clinical competence emerged as the sole significant independent predictor of compliance with standardized pain and sedation assessment (???? = 0.759, p < 0.001; 95% CI: 0.54 to 1.27). After multivariate adjustment, nursing culture was not significantly associated with compliance with standardized pain and sedation assessment (???? = -0.001, p = 0.993; 95% CI: -0.29 to 0.29). Conclusion: Clinical competence was the only independent predictor of compliance with standardized pain and sedation assessment among ICU nurses in multivariate model. Therefore, competency-based training and evaluation should be prioritized, while future longitudinal, multi-center studies should investigate the long-term effects of such interventions and other factors influencing compliance.