Mainstreaming neglected tropical diseases (NTDs) interventions in national health systems is one of the key strategies emphasized in the WHO Roadmap for NTDs. However, there is limited evidence on implementing the proposed mainstreaming approaches effectively. We used a participatory ranking methodology in Ethiopia, using consultative workshops with purposively selected stakeholders, including NTDs program leaders from the government and partners, primary health care (PHC) workers, and community leaders and volunteers. Our aim was to identify, rank, and contextualize mainstreaming challenges and strategies, which were then synthesized using the Primary Health Care Performance Initiative framework. Thirty-three stakeholders at the national, regional, district, PHC, and community levels participated in two consultative workshops conducted in the Adama and Shashemene towns in Ethiopia. The stakeholders identified 73 mainstreaming challenges related to service delivery (32 [43.8%]), inputs (22 [30.1%]), systems (18 [24.7%]), and outputs (1 [1.4%]). The top three most frequently cited and ranked challenges were poor data recording and reporting, poor drug management and logistics, and weak supportive supervision and monitoring. Among the 185 strategies identified to address these challenges, the three most frequently cited were establishing a strong, supportive supervision and monitoring system, continuous on-the-job training to build workforce competence, and performance-based motivation. Multifaceted NTDs campaign intervention mainstreaming challenges that are deep-rooted in the health system were identified. The suggested strategies to address them should be given due consideration not only to guide future mainstreaming efforts but also to facilitate health system strengthening.