Megiddo is a mysterious organization that have vast amounts of power and influences throughout the world. Their control spans from Moscow to Washington, D.C. and is largely clandestine, with only a handful of people being aware of it's existence.
The first mention of Megiddo is when Sam Fisher interrogates Lucius Galliard at the Lincoln Memorial in Washington, D.C. Galliard tells Sam that Megiddo influences a large number of different locations around the world, with control in Beijing, China and Moscow, Russia. Before Galliard can elaborate, however, he is shot and killed by an assassin from across the room. The assassin runs away, but Sam chases after him. The assassin eventually makes it to his vehicle and attempts to start the vehicle, causing it to explode and knock Sam on his back as he approached.
During Sam Fisher's infiltration into Third Echelon Headquarters, he discovered that Third Echelon director, Tom Reed, was a mole that was working with Megiddo. After interrogating Andriy Kobin, Sam finds out that Reed plans to assassinate President Patricia Caldwell because she wouldn't comply with Megiddo. Once Caldwell was dead, Vice President Calvin Samson (who works for Megiddo) would take her place, giving Megiddo even more influence over the United States of America. Thankfully, Sam and Grim prevented the assassination and Megiddo's plan was foiled.
In the next Splinter Cell installment, Megiddo plays a lot smaller role in the game.