High-copper alloy/nickel-based high-temperature alloy bimetallic structures are widely utilized in critical components, such as thrust chambers of liquid rocket engines, water cooling circuits for fusion reactor deflectors, and electromagnetic railguns. Among various methods for fabricating Cu/Ni bimetallic structures, laser directed energy deposition (LDED) is considered one of the most promising techniques for depositing nickel-based high-temperature alloys onto high-copper alloy surfaces. In the LDED fabrication process, substrates with uneven thicknesses are a common. The process is characterized by its multi-parameter, high-sensitivity, and non-equilibrium solidification characteristics. Consequently, variations in substrate size can significantly affect molten pool morphology and fabrication stability. This study examines the size effect of a single track of LDED Inconel 718 (In718) on a CuCr0.8 high-copper alloy substrate. The results indicate a pronounced size effect when using a high thermal conductivity CuCr0.8 substrate, particularly regarding substrate thickness. By reducing the thermal conductivity of the CuCr0.8 substrate, the size effect is mitigated, improving the process adaptability of LDED. These findings provide valuable data for the laser processing of surfaces with uneven thickness and high thermal conductivity. They are expected to support the fabrication of variable thrust liquid rocket engines and advance the field of interplanetary exploration.