After the final execution of Supernatural was penciled, the producers and cast described that the show had come to a natural ending, and most fans would perhaps agree with these sentiments, albeit reluctantly.
Supernatural has tried a few ramifications over the years, first with Bloodlines in 2014, and then again with Wayward Sisters in 2018. However, The CW rejected the option of an entire series.
The CW has enjoyed a successful spinoff from their other popular franchises, and the conclusion of Supernatural could tempt them to revisit the Wayward Sisters or focus on a new generation of hunters.
The Supernatural finale featured Sam Winchester’s son, growing up to be a hunter in his own right; There could be a Winchester Jr. series That said, The CW seems to believe that Supernatural is not viable without the Winchester brothers.
Fortunately, Supernatural is the kind of show where revivals and resurrections are always on the menu. A character can be eviscerated on the spot by a divine entity, and fans no longer blink at such antics.
There are several ways the Winchester brothers from Supernatural can return in the future. The easiest option would be for Jack to resurrect Dean to help his brother and nephew defeat a particularly tricky villain.