Background: Diarrhea is the second leading cause of death in children and poses a major threat to public health. It is mainly caused by pathogenic organisms of viral, bacterial, or fungal origin, two of which has been preventable via vaccination and has been identified as rotavirus and cholera. In 2020, India, Pakistan, and Bangladesh were among the top 10 South Asian countries with the highest mortality rates from childhood diarrhea. India and Pakistan are further listed by the WHO among the top five countries with the highest recorded mortality among children under five years old. Bangladesh has experienced the highest number of cholera epidemics. Vaccination is recommended as a potent preventive approach against rotavirus and cholera induced diarrhea and is considered the most cost-effective prevention method. However, despite their proven effectiveness, other factors appear to affect the impact of vaccination strategies in these countries. Therefore, this study aimed to explore these nonclinical factors. Methods: This study was conducted as a systematic review which involved the systematic search and selection of qualitative data from primary studies concerning the research topic which was developed using the SPIDER framework. The PRISMA tool was used to carry out this process, and the CASP was used to evaluate the methodological quality of each study. The combined data were then harmonized using meta-synthesis and analyzed thematically. Findings: Four themes emerged from the analysis of the study data: pre-vaccination strategy experience, post-vaccination strategy impact, opportunities for vaccination strategies, and threats to successful implementation of vaccination strategies. This formed the basis of the study discussion and expounded on the impact of vaccine strategies in the selected countries. Conclusion: The results of this study showed that providing the participants with correct information, vaccine education, willingness to learn despite poor knowledge, and access to vaccination are important solutions to the factors that surround the uptake and coverage of cholera and rotavirus vaccines in Bangladesh, India, and Pakistan as critical influencers of the prevalence of childhood diarrhea induced by rotavirus and cholera pathogens, respectively.