Vaccine-preventable diseases continue to be a major cause of morbidity and mortality among children under 5 years of age in Pakistan, and the country remains one of the last reservoirs of polio, posing a threat of viral spread within the region and globally. This structured review describes challenges in the achievement of vaccination targets and identifies arenas for policy and programmatic interventions and future research. Burdened with limited demand and inefficient vaccination services, the recently devolved Expanded Programme on Immunization (EPI) faces multiple hurdles in increasing immunization volumes, improving the quality of services and ensuring timely vaccination. The EPI requires multi-pronged, multi-level, coordinated interventions to improve programme functioning and to enhance vaccination uptake at community level. Additionally, a lack of rigorous scientific enquiry on vaccination services limits the introduction of well-developed, responsive interventions. The paper describes systemic bottlenecks, proposes potential solutions and suggests lines of further enquiry to understand and reduce the languishing immunization rates in Pakistan.