Abstract: Tailings and waste rock produced in metal mines are the most common industrial solid wastes all over the world, resulting in serious environmental and safety issues. Cemented paste backfill (CPB) is widely used for tailings management and stope treatment. CPB of total solid waste (TSW-CPB) was proposed on the basis of CPB of full-tailings. In the TSW-CPB process, thickened full-tailings, waste rock, and slag are mixed to prepare a paste that is filled into the stope. TSW-CPB can avoid the collapse of a stope, failure of the tailings storage facility, and landslide of a waste-rock yard, achieving the goal of “total waste to cure three harms.” The effects of solid fraction (SF), waste rock dosage (WRD), and glue powder dosage (GPD) on the slump (S), yield stress (τ₀), uniaxial compressive strength (UCS), and bleeding rate (BR) were investigated through orthogonal experiments. According to the scope of technical indicators specified in the National Standard of the People’s Republic of China “Technical specification for the total tailings paste backfill (GB/T 39489—2020),” the overall desirability function approach was used to conduct multiple response optimization of key TSW-CPB performance indicators. TSW-CPB was shown to have similar fluidity, transportation performance, mechanical properties, and bleeding performance to the CPB of full-tailings. The SF, WRD, and GPD affect the S, τ₀, UCS, and BR of TSW-CPB considerably. The SF has the most important influence on S and τ₀, while GPD has the most substantial impact on UCS and BR. Multiple response optimization yielded SF = 79.31%, WRD = 18.86%, and GPD = 3:20, with S = 25.45 cm, τ₀ = 100.49 Pa, UCS = 3.55 MPa, and BR = 1.50% as the corresponding responses. The optimal results can provide references for practical application, and the overall desirability function approach can be used in other mines to optimize multi objective CPB.