Background: Malaria remains a leading cause of morbidity and mortality in the Democratic Republic of the Congo, particularly in conflict-affected regions like the Maniema province. Amidst systemic supply chain failures and the regional emergence of Plasmodium falciparum resistance mutations, households are increasingly adopting local botanical alternatives. This study investigates the socio-economic and informational determinants of the reliance on Artemisia annua infusions in the Kalima Health Zone. Methods: A cross-sectional survey was conducted among 621 household heads employing an asset-based wealth index and multivariate logistic regression models. The study adhered to STROBE and ChecKAP reporting standards to ensure methodological transparency in evaluating Knowledge, Attitudes, and Practices regarding malaria management. Results: Results reveal a significant reliance on Artemisia annua infusions, with a prevalence of 77.8%. While 95.5% of respondents recognize malaria as a lethal threat, a critical “etiological gap” persists, with only 58.5% correctly identifying mosquito bites as the primary mode of transmission. Multivariate analysis identified television ownership (Adjusted OR = 2.736, 95% CI: 1.168–6.406, p = 0.020) and prior information exposure as the strongest independent predictors of health behaviors. Economic vulnerability is a primary driver: households in the lowest wealth tertile (64.7%) and those with large families (≥16 members, 77.8%) are significantly more likely to utilize infusions. Although 88.2% of users report high community-perceived tolerance, this local confidence exists in direct tension with international concerns regarding sub-therapeutic dosing and potential selection pressure for resistance. Conclusion: The reliance on Artemisia annua in Maniema functions as a rational socio-economic coping mechanism rather than a rejection of scientific medicine. This “localized resilience” highlights critical gaps in the formal healthcare infrastructure and the supply chain for subsidized ACTs. Effective malaria control in fragile settings requires bridging the access gap for validated therapies while integrating community practices into standardized genomic and clinical surveillance systems.