Lassa virus (LASV) has increasingly been recognised as a significant public-health pathogen transmitted by rodents. LASV infection leads to life-threatening Lassa fever, which has high potential for severe morbidity and mortality. There have been several scientific efforts to understand the genomics and ecological epidemiology of Lassa. However, very limited studies have focused on the short- and long-term impacts of environmental factors, human behaviours and rodent activities on LASV transmission dynamics and control. Recently, a very plausible and ideal way to address the Lassa epidemic has been considered through the One Health approach. The One Health system of intervention is capable of providing better and comprehensive information necessary to address the complex interplay between human, ecological, and environmental determinants of LASV transmission, persistence and re-emergence. Thus, the aim of this article was to review critically the impacts of various environmental factors on rodent infestations, LASV transmission and how human activities contribute to the persistence of Lassa with regard to exploring how they could be harnessed for better understanding of Lassa prevention and control through a concerted One Health approach.