It's basically confinement, in both magnetic and inertial fusion schemes. You are trying to force positively charged nucleii very close together, so that the nuclear strong force takes over - depending on the nucleii, the resulting fused mass is energetically favorable, so that energy is liberated in the process provided you put in enough energy up front to overcome the electrical repulsion of the separate nucleii. You can do this with very low efficiency very easily, just from random chance that two nucleii come together and fuse - doing this efficiently, so that you get more energy/power out compared to all the energy/power you put into all the nucleii, is the rub. Stars use gravity to overcome coulomb repulsion and generate power, but we can't use this at the scale of human-made devices.
Every time we humans have come closer to this confinement condition, we've uncovered another complicated collective phenomenon that makes it more difficult than we thought, so that fusion energy power plants have always been 20 years in the future.
Fission power plants, in contrast, are comparatively easy because they use uncharged neutrons to break up nucleii, so there's no coulomb barrier to overcome.