In open-pit mining operations where activities are conducted below water table or close to surface water bodies, the mine is potentially faced with dewatering and slope stability challenges. Appropriate evaluation of slope stability to obtain adequate slope safety factor has continuously been the centre of geotechnical research locally and internationally. This paper evaluates the influence of buoyant action propagated by groundwater and surface (GW-SW) interaction on pit slope designed in multi-layered fractured rock with complex hydrology using Hydrogeological-Stratigraphic-Structural Assessment (HSSA) at the Nsuta Manganese Mine in Ghana). LEM analyses of the Pit C-western slope estimated an overall factor of safety (FOS) of 1.1, probabilities of failure (POF) of 7.5% and the reliability index (RI) of 1.4 in the slope stress field. However, when the groundwater was introduced, the slope FOS was reduced to 0.13, POF of 100.0% and (RI) of 0.00 indicating failure. FEM numerical model points to the location of maximum shear strain and total displacement in the argillite zone within the rock mass. The FEM seepage analysis model estimated groundwater pore pressure data along the critical slide surfaces from the crest of the slope to the bottom of the rock slope ranging between 250 kPa and 4250 kPa with an average pore pressure of 2250 kPa within the pit slope. This proposed HSSA approach used in the study provides innovative insights into the percentage failure contribution of the individual lithologies to the overall combined lithological susceptibility of the slope under stress and groundwater failure mechanisms, pointing out Ru ratio in pit slope stability estimation as inadequate.