Abstract: During open-pit coal mining, coal pillar retention is an important measure to improve the stability of dump slopes. Existing studies on the determination of coal pillar retention width are mostly based on theoretical analysis, stress distribution, and plastic zone evolution characteristics, with insufficient consideration given to slope failure modes under inclined weak foundation conditions, and both safety and economy have not been simultaneously considered in determining the coal pillar retention width. Taking the east dump slope in the second mining area of Zhundong Open-Pit Mine of CHN Energy Xinjiang Zhundong Energy Co., Ltd. as the engineering background, numerical simulation methods were adopted to analyze the displacement and maximum shear strain increment characteristics of the dump slope. The results showed that the shear deformation of the dump slope was mainly concentrated in the weak floor layer and the slope toe area, and the potential slip surface developed along the weak floor layer and tended to become continuous. Based on these findings, two types of potential slope failure modes of the dump slope under inclined weak foundation conditions were identified, including overall sliding controlled by the weak floor layer and local sliding affected by the coal pillar retention width. Stability analyses of the slope under different coal pillar retention widths were then carried out based on the two potential slope failure modes. The local stability and overall stability of the dump slope were improved by enlarging the coal pillar bench width and haulage berm width, respectively, and the safe slope configurations under different coal pillar retention widths were determined. On this basis, the coal loss cost and secondary stripping cost were calculated. It was found that, with the increase in coal pillar retention width, the total cost of coal loss and secondary stripping first decreased and then increased. According to the principle of "safety and stability first, followed by economic rationality", the reasonable coal pillar retention width for the dump slope was determined to be 40–80 m, which not only satisfied the slope stability requirements but also achieved favorable economic benefits.