In this study, landfill sludge (LS) was excavated from a 10 year old full-scale sludge landfill and used to investigate effects of dosage on sludge dewaterability, rheological properties and extracellular polymeric substances (EPS) variations by FeCl₃-lime conditioning. LS had lower content of organic matters (0.28) and smaller particle size than excess sludge (ES), and greatly lower viscosity and high flowability. The suitable concentration of LS for conditioning (107.2–118.6 g/L) was much higher than that of ES (34 g/L) by rheological analysis. Both FeCl₃ and lime improved dewaterability of LS and caused decline of slime and loosely bound EPS (LB-EPS). FeCl₃ destroyed proteins in slime and LB-EPS owing to coagulation and acidification effects, weakened internal structure strength, and thus improved dewaterability. Lime addition caused alkaline hydrolysis of polysaccharides in slime and LB-EPS, reduced viscosity and flowability, and improved flowability and dewaterability for LS. The optimal dosage for dewatering using 57.6 mg lime/g dried solids (DS) and 53.6 mg FeCl₃/g DS was obtained by using an integrative response surface methodology (RSM) coupled nonlinear programming approach under water content constraint of 55%. The integrative optimization achieved 26.0% cost saving in comparison to RSM optimized condition.