George Washington and Capital will battle for the girls team championship, with No. 5 Ripley expected to win the boys team title.
Behind the Ripley boys, No. 7 Oak Hill, GW and Greenbrier East will compete for two spots to advance.
Capital Coach Jared Smith said don't discount the Cougars, though.
"I think that my boys are peaking at the right time," he said. "They're going to give every thing that they have to go for that final spot."
For the Patriots, junior Matthew Brafford will lead the way. Brafford looks to be the favorite for the individual regional championship, but will need to contend with Greenbrier East's Levi Snedegar and Wes Stowers, of Oak Hill. Each rank within the state's top eight for Class AAA.
"He fully expects to go out and win," Patriots Coach Nick Bias said of Brafford. "He's never won regionals before, he's never been a regional champ before, but he wants to go out and win, make a statement."
In the girls race, Capital sophomore Peyton Panger, rated seventh-best in Class AAA, will be the favorite for the individual title. Other individuals expected to contend near the top include Ripley's Ali Cunningham, Emily Fedders, of Beckley, Shady Spring's Taylor Jackson and Adrienne Arnold, of GW.
No girls team within Region 3 is ranked, but competition will be thick between evenly matched GW and Capital. Ripley, Shady Spring and Greenbrier East will contend for the final spot.
"We have to be on our toes and ready," Smith said. "Hopefully, we'll come out with a good performance. I want the kids to go to the state meet and have fun, but I would be lying to you if I told you I didn't want that regional championship."
Class AA/A Region 4
Buffalo appears poised to take the boys team title as the Bison enter ranked fifth statewide, though ninth-ranked Charleston Catholic will look to contend, too, with Ravenswood and Roane County following.
Senior Dylan Rich will lead Buffalo and also threaten for the individual championship, though Scott's Will Shaffer is the favorite to claim the title.
Charleston Catholic boasts a solid one-two punch in senior Marcus Black and junior Caden McClanahan. Black is ranked sixth in the state and eager to return to state after an 11th place showing last year.
On the girls side, No. 2 Scott factors to be the favorite behind senior Brittany Green, who will contend for the individual title with Ravenswood's Hailey Miller.
Behind Scott and Ravenswood, Charleston Catholic and Nicholas County will battle for the final spot.
Should the Irish not advance as a team, Catholic's Sami Harris and Annie Crockett will be contenders as individuals.