Sustainable humanitarian supply chain (SHSC) management enables effective and efficient responses to natural and human-made disasters. Existing literature falls short of offering decision support (DS) models to address the barriers and strategies to designing SHSC. To this end, this study develops a DS model that identifies and prioritizes the barriers to SHSC and determines optimal strategies for mitigating those barriers. This study adopted both qualitative and quantitative approaches. As part of the qualitative approach, a field study was applied using in-depth interviews to determine the barriers and corresponding strategies, while under the quantitative approach, a quality function deployment (QFD) integrated optimization technique was used to prioritize barriers and determine optimal strategies to mitigate the SHSC barriers. The study found that a lack of contingency planning, the prevalence of corruption and political interference, and a lack of social and environmental awareness are the most important barriers, while logistics outsourcing, supply chain (SC) performance management, and SC flexibility are the most essential strategies. We also found that our DS model is highly flexible and can be adapted under different scenarios, which makes the model applicable to different contexts. This study has a significant contribution to literature and practice. We developed a novel decision model that captured cost savings and leveraged both cost and time savings from interrelated strategies to determine the best optimal strategy while applying QFD-integrated optimization modeling. The paper’s findings will assist humanitarian SC managers in designing an effective, efficient, and sustainable humanitarian SC.