<p>Effective humanitarian logistics management is critical for pharmaceutical supply chain resilience during public health emergencies. Understanding the relative contributions of internal capabilities versus external constraints to humanitarian logistics performance remains limited, particularly in resource-constrained settings. This study examines the performance of humanitarian logistics in Ethiopia’s public pharmaceutical supply chain, with a focus on identifying key factors affecting logistics efficiency. It seeks to provide actionable insights to enhance the management of pharmaceutical logistics during public health emergencies. We conducted an explanatory cross-sectional study from September 10 to October 9, 2021, involving 92 professionals from the Ministry of Health, the Ethiopian Pharmaceuticals Supply Services, and the Ethiopian Public Health Institute. Data were collected using a semistructured questionnaire, which assessed perceived performance across five key indicators: reliability, responsiveness, agility, cost, and asset management. All dependent and independent variables represent perceived, rather than objectively measured, performance and drivers. Statistical analyses included descriptive statistics, the Kruskal–Wallis <i>H</i> test, and regression analysis. Qualitative insights from seven key informant interviews triangulated and contextualized the quantitative findings. The study revealed a generally high level of performance across reliability, responsiveness, agility, cost, and asset management (mean scores 3.48–3.68). However, comparatively lower mean scores for responsiveness suggest persistent challenges in meeting time-sensitive delivery requirements. The key determinants of logistics performance were the implementation of information and communication technology (ICT), adequate donor funding, and the suitability of environmental, socioeconomic, and infrastructural conditions. Predictive analysis further indicated that external factors were significantly associated with perceived humanitarian logistics performance (<i>β</i> = 0.872, 95% CI [0.776, 0.961], bootstrap <i>p</i> &lt; 0.001), with the predictive model explaining a variance of substantial variance (nine-predictor in-sample <i>R</i>² = 0.795; fivefold nested-CV ridge <i>R</i>² = 0.752 ± 0.069; CV-RMSE = 0.325 ± 0.037). The cross-validated estimate should be regarded as the true measure of out-of-sample predictive accuracy; all coefficients are standardized associations based on perceptual data and should not be interpreted causally. Meanwhile, internal organizational capabilities showed no statistically significant association (<i>β</i> = 0.034, 95% CI [−0.080, 0.143], bootstrap <i>p</i> = 0.547). After Holm correction across the nine predictor domains, only donor funding remained statistically significant (<i>β</i> = 0.366, Holm <i>p</i> = 0.004). Qualitative analysis identified four critical barriers: strategic planning deficits, fragmented coordination, infrastructural bottlenecks, and financial system inefficiencies. The study underscores the importance of improving logistical infrastructure, addressing environmental and socioeconomic challenges, securing consistent donor support, and advancing ICT systems to optimize humanitarian logistics. While internal organizational capabilities had minimal impact, they should not be overlooked. These findings provide valuable recommendations for policymakers and stakeholders to strengthen Ethiopia’s humanitarian logistics systems and improve the timely delivery of pharmaceuticals during emergencies.</p>