The second season of Supergirl ended with Kara (Melissa Benoist) making the decision to use a device that would lace the air with trace amounts of lead. Not enough to hurt humans, but it would be toxic to Daxamites. This made a lot of sense, since they were trying to fight off a Daxamite invasion lead by Rhea (Teri Hatcher). But it also made the Earth deadly to Supergirl's love interest Mon-El (Chris Wood), who she helped into the ship that brought him to Earth and he flew off into space — only to disappear into a portal of some kind.
That doesn't end the Mon-El story, though. According to TVLine, executive producer Robert Rovner says that Mon-El's whereabouts remains one of the central mysteries of the new season, we won't have to wait long before seeing him back in action. He returns to National City after a little time jump, to find that Kara has decided that the cost of being human is too much to handle and she is solely focused on her work at the DEO. This puts a huge strain on all of her relationships.
Rovner teased a few other things including Alex (Chyler Leigh) and Maggie (Floriana Lima) going on a trip together and Maggie's father (Carlos Bernard) coming to town. We'll get more Cat Grant (Calista Flockhart), who wants to push Kara in the right direction. James (Mehcad Brooks) is going to get a love interest this year besides his shield. And we'll get to see a new aspect of J'onn (David Harewood) as we are introduced to his father, M'yrnn (Carl Lumbly). A nice Easter egg there, as Lumbly voiced J'onn J'onzz on the Justice League animated series.
Finally, Rovner promised that the show will be thoroughly exploring the season's big bad, Reign (Odette Annable), unlike they've done with any other villain so far.
Supergirl Season 3 debuts October 9th on the CW.