Clinical research conducted to Good Clinical Practice (GCP) standards is increasingly being undertaken in resource-constrained low-income and middle-income countries (LMICs) settings. This presents unique challenges that differ from those faced in high-income country (HIC) contexts, due to a dearth of infrastructure and unique socio-cultural contexts. Field experiences by research teams working in these LMIC contexts are thus critical to advancing knowledge on successful research conduct in these settings. The Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine has operated in The Gambia, a resource-constrained LMIC for over 70 years and has developed numerous research support platforms and systems. The unit was the lead clinical collaborator in a recently completed Expanded Program on Immunization Consortium (EPIC) study, involving a multicountry collaboration across five countries including the USA, Canada, Belgium, Papua New Guinea and The Gambia. The EPIC study recruited and completed follow-up of 720 newborn infants over 2 years. In this paper, we provide in-depth field experience covering challenges faced by the Gambian EPIC team in the conduct of this study. We also detail some reflections on these challenges. Our findings are relevant to the international research community as they highlight practical day-to-day challenges in conducting GCP standard clinical research in resource-constrained LMIC contexts. They also provide insights on how study processes can be adapted early during research planning to mitigate challenges.