In this work, we employ response surface methodology and finite element simulation to optimize the preparation of carbon blocks via cold isostatic pressing. A response surface is developed to analyze two responses of the carbon block green body (apparent porosity and compressive strength) and optimize four factors of the fabrication process (binder content = 14 wt%, maximum particle size = 1 mm, Andreasen distribution modulus = 0.33, and compaction pressure = 200 MPa) to achieve an apparent porosity of 10.02% and a compressive strength of 46.26 MPa. Optimized parameters are found to improve micropore content, and SEM characterization reveals that the resulting microstructure consists of evenly distributed, closed circular pores, with a pore size distribution of 0.28–9.04 μm determined via mercury intrusion porosimetry. For the first time, a three-level structural model of the raw carbon block material as binder-coated particles with surface-adhered fine powders is established to carry out finite element simulations of the cold isostatic pressing process, with which mechanisms for the densification and microporosity of the carbon block are examined. Response-surface optimization of the cold isostatic pressing process facilitates reduction and uniform distribution of stress and strain within the particle-based composite, as well as improvements in relative density, reductions in pore size range, and increases in uniform microporosity. Particle size is identified as a key parameter influencing deformation under compaction, subsequent pore formation, and the resulting performance of carbon blocks.