A country's preparedness for a prompt and successful implementation of vaccination programs plays a pivotal role in disease control and prevention. As it stands now, Afghanistan seems to be ill-prepared to embrace a successful implementation of the COVID-19 vaccination program because of a spate of challenges. These include, but are not limited to, the insufficient number of vaccinators, a dearth of fully integrated functioning cold chain, challenging geographical barriers, cultural issues, insecurity, and protracted conflict. The COVID-19 infodemic along with vaccine mistrust in the country will lead to a pervasive public vaccine hesitancy in Afghanistan, which will present serious obstacles to the COVID-19 immunization efforts. The politicization of the Ministry of Public Health (MoPH) and the complaints of embezzlement and misuse of the pandemic aid have already eroded public trust during the pandemic. To ensure a large-scale and equitable distribution of COVID-19 vaccines, the cold chain infrastructure should be strengthened, and the immunization personnel trained. Antivaccination propaganda and misinformation should be tackled with effective communication approaches and effective community engagement, which consider culturally relevant messages appropriate to the culture and people. The allegations of corruption should be addressed to revive public trust in public health interventions, including COVID-19 vaccination.