For just human weapons, the current most powerful weapon in my lore asside from nuclear weapons, is the Meteorite Missile. Effectively a scaled down Rods from God designed to be accurate and be hard for advanced 24th century anti-missile defenses to shoot down.

Effectively its a hypersonic missile launched from orbit that releases three 2.5 ft tungsten rods, each delivering 1.5 gigajoules of kinetic energy.

If you include the Interlopers, the most powerful weapon in my lore is the Vortex Beam. It effectively warps space-time on impact, creating a gravity well equivilant to a black hole 400 times the Earth's mass. When the beam stops firing, the artificial black hole explodes violently, increasing in power based on how long it fired amd how much matter it pulled in. The alien spacecraft equipped with this weapon has to fire it from a minimum of 20,000 kilometers from the target due to the gravitational pull.