Theoretical–computational studies of table-top laser-driven nuclear fusion of high-energy (up to 15 MeV) deuterons with , , and D nuclei demonstrate the attainment of high fusion yields within a source–target reaction design. This constitutes a source of Coulomb-exploding deuterium nanodroplets driven by an ultraintense femtosecond near-infrared laser and a solid hollow cylindrical target containing the second element. The source–target reaction design attains the highest table-top fusion efficiencies (up to per laser pulse) obtained to date. The highest conversion efficiency of laser energy to nuclear energy (– for table-top DD fusion attained in the source–target design is comparable to that for DT fusion currently accomplished for ‘big science’ inertial fusion setups.