The many challenges in the Eastern Mediterranean region put the involved countries at risk of polio transmission and affect their ability to meet progress targets in eliminating vaccine-preventable diseases. The Global Health Development (GHD) and Eastern Mediterranean Public Health Network (EMPHNET) are working together on the project “Strengthening sustainable public health capacity in the Eastern Mediterranean region for polio eradication and routine immunization activities” with an overall goal of improving routine immunization, eradicating poliovirus, and controlling/eliminating or eradicating other vaccine-preventable diseases in the Eastern Mediterranean region. The aim of this manuscript is to describe the project and the achievements of GHD/EMPHNET over the last 3 years (2016-2018) to build effective surveillance and immunization systems in the Eastern Mediterranean region through the development of a sustainable and competent public health system to eradicate polio and control/eliminate vaccine-preventable diseases. This project assists the targeted Eastern Mediterranean region countries to build effective surveillance and immunization systems in an effort to expand their capacities to eradicate polio and control/eliminate other vaccine-preventable diseases. The project is streamlined with the Global Polio Eradication Initiative, the Centers for Disease Control and Prevention’s Strategic Framework for Global Immunization 2016-2020, and the Polio Eradication and Endgame Strategic Plan 2013-2018. The project also supports the Global Health Security Agenda by focusing on efforts to accelerate progress toward a world safe and secure from infectious disease threats. Project activities were designed to respond to countries’ needs and assist them in building their institutional and workforce capacity to effectively plan, implement, and evaluate activities to eradicate polio and strengthen routine immunization activities. The project activities covered a set of areas including surveillance of acute flaccid paralysis and other vaccine-preventable diseases, family and community engagement, workforce capacity building, improvement of data quality, management and use of information systems, use of polio assets to control/eliminate other vaccine-preventable diseases, support of countries to develop national strategies, piloting of innovative initiatives, program evaluation and accountability, and immunization strengthening. The project adopts the Global Polio Eradication Initiative strategies for assisting countries to strengthen routine immunization services, maintain highly sensitive acute flaccid paralysis surveillance, and sustain polio eradication functions.