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International non-governmental organizations (NGOs) are widely involved in initiatives aimed at advancing socioeconomic development in the Global South, yet their impact varies considerably. We examine what enables some NGOs to achieve sustained positive outcomes in complex, unfamiliar environments, while many others struggle to do so. Drawing on a seven-year ethnographic field study of six international NGOs in two East African slums, we identify stark differences in how these organizations have engaged with local communities. Most NGOs in our sample adopted a top-down, standardized approach that privileged externally defined solutions, embraced a paternalistic logic, and treated diverse local communities as homogeneous. This approach undermined organizational learning, damaged local reputations, and weakened community relationships, ultimately limiting long-term effectiveness. In contrast, one organization in each site adopted what we term an anthropological mode of organizing: a set of interlocking norms and practices characterized by a focus on ethnographic learning, cultural and epistemic humility, and keen attention to ethnic heterogeneity. This mode of organizing yielded nuanced contextual insights, built trust with local communities, and facilitated engagement with different ethnic groups, thereby fostering the co-creation of tailored, community-driven social innovations. Our study helps explain why some NGOs achieve more sustained impact and co-creation than others. It also challenges a common portrayal of urban informal settlements in the Global South as mere “poverty contexts,” and shows how humility extends beyond an individual attribute to a collective, organizational posture enacted through organizational routines that prioritize local knowledge.