Ash Ketchum has had many different companions throughout the Pokémon anime, but few longtime fans of the series will forget the original trio that traveled the Kanto region together. During Pokémon Indigo League, Ash is accompanied by Brock and Misty. Misty was a popular female character who stood up to challenges and had no problem voicing her opinions about situations the group found themselves in. Because of this, many were sad to see Misty go when she split from Ash and Pikachu later in the series, and lapsed fans likely wonder if Misty ever came back.
Misty is a Water-type Pokémon trainer and Gym Leader of the Cerulean City Gym in Pokémon's Kanto region, along with her three sisters. Misty first appears in Episode 003 of the series, when Pikachu destroys her bike. She initially teams up with Ash and Pikachu in an attempt to be reimbursed for the ruined bicycle. Then, in her dedication to hold the pair accountable, she sticks with Ash and Pikachu on their Pokémon adventures through the Kanto region.
Misty leaves Ash behind to become the sole Gym Leader of the Cerulean City Gym in Episode 273, according to Bulbapedia, after a long journey in the Kanto and Johto regions. While Misty seems genuinely sad to be leaving her friends behind, it won't be the last time she and Ash bump into each other during the Pokémon anime.
Pokémon's Misty Makes Many Reappearances In Regions After Johto
Misty isn't gone for good when she takes on her Gym Leader responsibilities, making cameo appearances in Pokémon's Ruby and Sapphire series, as well returning for bigger roles with Brock in the Sun and Moon series. When Ash visits the Kanto region, for example, she and Brock help compare Sun and Moon's Alolan forms of Pokémon to their Kanto forms. She and Ash also have a chance to face off again during his visit to Cerulean City. However, despite her return to the stage during the Sun and Moon anime, Misty is again absent in Pokémon Journeys. This could be due to a lack of clarity on where Ash has traveled in the newest installment of the Pokémon series - and whether he has met Brock and Misty at all, yet.
While her cameos in more recent seasons of the show have been brief, Misty's reappearances have allowed her to continually delight fans who have stuck with the series since its start. Viewers have had the chance to see her design change to fit different Pokémon regions, as well as to check in on what she has been up to. Though it is unlikely that she will travel with Ash again as a future companion for a new region, hopefully Pokémon will give Misty more cameo appearances as Ash checks in with old friends.
Source: Bulbapedia