Vector control (VC) is one of the strategies employed to manage African trypanosomoses. This study aimed at assessing the effectiveness of a VC campaign against Glossina palpalis palpalis using tiny targets (TTs) impregnated with insecticide in an isolated, protected forest in Abidjan, Côte d'Ivoire, while considering ecological, genetic, and operational factors. Between January 2020 and September 2022, 2,712 TTs were deployed at 684 sites, covering a total area of 1.7 km2. VC monitoring was conducted using Vavoua traps during 12 evaluation surveys, between June 2020 and March 2023. Five months after the initial TT deployment, tsetse fly density had decreased by 98.53%. Although tsetse density remained low due to TT redeployment and reinforcement, there was a significant increase a few months after the last redeployment. VC appeared to have minimal impact on the genetic structuring of G. p. palpalis. This suggested recruitment of local surviving tsetse flies all along the VC campaign due to a low probability of tsetse coming into contact with TTs, or to the evolution of behavioral or physiological resistance to control efforts. The genetic study revealed that one of the microsatellite markers used, the GPCAG locus, exhibited a selection signature possibly in response to VC. This could partly explain the challenges encountered in eliminating a seemingly isolated tsetse population thriving in a particularly favorable habitat.