Groundwater resources in the Kou sub-basin of southwestern Burkina Faso play a critical role in supporting domestic water supply, agriculture, and industry in and around Bobo-Dioulasso, the second-largest city in Burkina Faso. This study synthesizes over three decades of research on groundwater vulnerability, recharge mechanisms, hydrochemistry, and residence time across the region’s sedimentary aquifers. The Kou basin hosts a complex stratified system of confined and unconfined aquifers, where hydrochemical analyses reveal predominantly Ca–Mg–HCO3 facies, alongside local nitrate (0–860 mg/L), iron (0–2 mg/L) and potassium (<6.5 mg/L–190 mg/L) contamination. Vulnerability assessments—using parametric (DRASTIC, GOD, APSU) and numerical (MODFLOW/MT3D) models—consistently indicate moderate to high vulnerability, especially in alluvial and urban/peri-urban areas. Isotopic results show a deep recharge for a residence time greater than 50 years with deep groundwater dating from 25,000 to 42,000 years. Isotopic data confirm a vertically stratified system, with deep aquifers holding fossil water and shallow units showing recent recharge. Recharge estimates vary significantly (0–354 mm/year) depending on methodology, reflecting uncertainties in climatic, geological, and anthropogenic parameters. This review highlights major methodological limitations, including inconsistent data quality, limited spatial coverage, and insufficient integration of socio-economic drivers. To ensure long-term sustainability, future work must prioritize high-resolution hydrogeological mapping, multi-method recharge modeling, dynamic vulnerability assessments, and strengthened groundwater governance. This synthesis provides a critical foundation for improving water resource management in one of Burkina Faso’s most strategic aquifer systems.