Implementing the International Health Regulations (IHR 2005) can be a cumbersome process, and costs vary widely from country to country. To support facilitating this complex work, experts from Resolve to Save Lives tested several new tools designed to estimate the resources needed for implementing the IHR. Using Nigeria’s National Action Plan for Health Security (NAPHS) as a case study, we compared cost estimates generated through the World Health Organization (WHO) Costing Tool, Georgetown University’s IHR Costing Tool, and CDC’s Priority Actions Costing Tool (PACT). While the tools suggested similar activities for implementation, cost estimates varied due to differences in procurement and human resource needs. We found that a strategic approach, prioritizing major cost drivers based on resource availability, could help accelerate the implementation of health security plans.