Despite the deployment of several effective control interventions in central-western Senegal, residual malaria transmission is still occurring in some hotspots. To better tailor targeted control actions, it is critical to unravel the underlying environmental and geographical factors that cause the persistence infection in hotspot villages. "Hotspots villages" were defined in our study as those reporting more than six indigenous malaria cases during the previous year. A total of ten villages, including seven hotspots and three non-hotspots, were surveyed. All potential mosquito breeding sites identified in and around the ten study villages were regularly monitored between 2013 and 2017. Monitoring comprised the detection of anopheline larvae and the collection of epidemiological, hydrogeological, topographical, and biogeographical data. The number of larval breeding sites described and monitored during the study period ranged from 50 to 62. Breeding sites were more numerous in hotspot sites in each year of monitoring, with 90.3% (56/62) in 2013, 90.9% (50/55) in 2014, 90.3% (56/62) in 2015 and 86% (43/50) in 2017 (Fisher exact test; p = 1). In the non-hotspot areas, the data for the same years were, respectively, 9.7% (6/62), 9.1% (5/55), 9.7% (6/62) and 14% (7/50) (p = 1). The Hotspot villages were characterized mostly by saline or moderately saline hydro-morphic and halomorphic soils allowing water retention and a potential larval breeding sites. By contrast, non-hotspot villages were characterized mainly by a high proportion of extremely permeable sandy-textured soils, which due to their porosity had low water retention. The annual number of confirmed malaria cases was correlated with the frequency and extent of breeding sites. Malaria cases were significantly more frequent in the hamlets located near breeding sites of An. gambiae s.l., gradually decreasing with increasing remoteness. This study shows that the characteristics of larval breeding sites, as measured by their longevity, stability, proximity to human habitation, and their positivity in Anopheles larvae are likely determining factors in the persistence of malaria hotspots in central-western Senegal. The results of this study shed more light on the environmental factors underlying the residual transmission and should make it possible to better target vector control interventions for malaria elimination in west-central Senegal.