A post on the official Facebook page of ToeJam & Earl (posted a week ago, sorry about our tardiness) revealed that not only is work being done on a fourth game in the series (we don't really count the Menacer mini-game Ready, Aim, Tomatoes as a main entry in the series), but we'll soon hear the first concrete details.
"Greetings from Funkotron! We haven't been posting as often lately because we've gotten really busy with the new TJ&E game. We will be making some announcements in a probably 3 or 4 weeks, when we have something we can show, and will be able to share lots of information with you."
The game is in development at HumaNature Studios (Doki-Doki Universe), and it will be interesting to see whether the game retains the topdown roguelike stylings of the original or opts for another approach. Will it be a Kickstarter project or will a publisher be involved?