Molecular engineering of high energy barrier U eff in single-molecule magnets (SMMs) of general composition Mo III k V II m based on orbitally-degenerate pentagonal-bipyramidal [Mo III (CN) 7 ] 4− complexes with unquenched orbital momentum and high-spin V(II) complexes is discussed. In these SMMs, the barrier originates exclusively from anisotropic Ising-type exchange interactions −J xy (S i x S j x + S i y S j y) − J z S i z S j z in the apical cyano-bridged pairs Mo III-CN-V II , which produce a double-well energy profile with a doubly degenerate ground spin state ±M S. It is shown that the spin-reversal barrier U eff is controlled by anisotropic exchange parameters J z , J xy, and the number n of apical Mo III-CN-V II groups in a SMM cluster, U eff~0 .5|J z − J xy |n; it can reach a value of many hundreds of wavenumbers (up to 741 cm −1). This finding provides a very efficient straightforward strategy for further scaling U eff to high values (>1000 cm −1) by means of enhancing exchange parameters J z , J xy , and increasing the number of [Mo III (CN) 7 ] 4− complexes in a SMM molecule.