This is the only game in the whole franchise where we actually see Kane in-game. He have been the main villain in the Full-motion-videos throughout the franchise, but this is actually the first time we see a unit model and avatar of the character Kane in the actual game.
Joseph D. Kucan has played the villain 'Kane' in every single installment of the Tiberium franchise.
This is the first Command & Conquer game where you can actually train and control Visceroids. They were always a neutral non-controllable critter unit in the earlier games.
Initially, EA Los Angeles made an experimental online-only game called Command & Conquer: Arena, meant for the Asian market. At some point in 2009, Electronic Arts higher-ups ordered to convert it to a mainline game, add a single-player campaign and ship it as such. The decision was controversial even within EA Los Angeles, leading certain developers like designer Greg Black to leave the company. Arena's existence was unknown to the Command & Conquer community until 2010, when Greg Black outed some information on it, certain concept images leaked, and Richard Taylor posted an unreleased but finished CGI trailer for the game.
Customers who pre-ordered Command & Conquer 4: Tiberian Twilight got a prequel mission called "Night Moves". Access to the mission was tied to the player's account, but could be played in co-op as long as at least one player had an account with that mission attached to it. Victory Games added the mission to the accounts of all willing players who posted on the official Command & Conquer forums from 2011 until their closure in October 2013.