The concept of maximizing the D-D fusion neutron yield from the laser-heated large volume of cluster medium by matching the focal spot size and cluster plasma structural scales to the laser pulse intensity was confirmed. For this purpose, the three-dimensional particle-in-cell GEANT4 simulations have been performed by zoning of the large interaction domain. While considering a small domain of the entire interaction volume, which is partitioned into successive zones along laser propagation direction, a special algorithm was proposed allowing to reconstruct the integral spectrum of deuterons and D-D neutron yield. We demonstrate that it makes possible to specify high-performance laser–cluster neutron source following this concept. For example, for the submicron heavy water droplets heated by femtosecond laser pulse of the intensity 3×1019 W/cm2 a D-D neutron yield may reach 107 neutrons per 1 J of deposited laser energy if the intensity contrast ratio prevents premature cluster destruction. Such yield is considerably higher than achieved to date for microstructured targets.