The optimization of the programming voltage and the dimensions of antifuse bitcells is a design challenge due to antagonistic parameters. An optimization approach is presented using a time-dependent dielectric breakdown (TDDB) model. Fowler-Nordheim wear-out current and TBD power-law models are identified using electrical characterizations performed on antifuse bitcells fabricated in standard 40-nm CMOS. The TDDB model allows the calculation of the programming voltage according to a targeted TBD and the antifuse bitcell dimensions. As a result, it was shown that the lowest programming voltage is obtained for a small capacitor, whereas the size of the drift transistor has a second-order impact.