Suicide Squad Isekai opens in Gotham with the Joker and his best girl, Harley Quinn, tearing through the streets with sacks full of cash and the law in hot pursuit. The Joker manages to escape, but the night ends with Harley being captured by a mysterious, katana-wielding woman.
Meanwhile, Amanda Waller, the hard-line head of the government security organization A.R.G.U.S., has commandeered a team of supervillains for a ruthless mission into another world. After losing contact with the first suicide squad sent through the portal, Amanda sends Deadshot, Peacemaker, Clayface, King Shark, and Harley as replacements. Yet the mission goes wrong almost immediately when their helicopter crashes in the middle of a battle between horse-mounted troops and vicious orcs.
With all of the accompanying A.R.G.U.S. members dead on impact, the villains break free of their shackles and rampage through the army of orcs, unwittingly aiding the human soldiers—only to be rewarded with imprisonment. Now bound by magic-infused shackles, Harley and company must hurry back to the portal they came from, or else the bombs A.R.G.U.S. implanted in their necks will detonate. Caught between a hostile fantasy world, their own violent instincts, and Waller's lethal leverage, the squad has to survive long enough to find a way home.