As Locker looks to lead the Titans to their first 2-0 start since 2008 in their home opener, Romo will try to bounce back and help the defensively challenged Cowboys avoid their first 0-2 start in four years Sunday.
Locker led the way during Tennessee's strong start last season with six touchdowns and no interceptions before suffering a hip injury against the New York Jets in Week 4.
The Titans had gotten off to a 3-1 start, but then dropped eight of 12 while Locker missed nine games with two injuries.
With the fourth-year quarterback finally back to full health, Tennessee (1-0) is thinking big following Sunday's 26-10 road victory over a Kansas City team that won 11 games and reached the postseason a year ago.
''We didn't go in there with the idea 'it's us against the world, nobody's picking us to win,''' coach Ken Whisenhunt said after his first victory with the Titans. ''We went in there with the idea if we play football the way we're supposed to, we're going to win the game.''
Locker completed passes to eight players, going 22 of 33 for 266 yards and two touchdowns in one of his best performances as a pro. He posted a 111.4 rating that was his third-best mark in 19 career starts and second only to Peyton Manning in the AFC in Week 1.
The Titans also held the ball for 37 minutes, 44 seconds for their highest time of possession since November 2009. They racked up 162 of their 405 total yards on the ground, led by Shonn Greene with 71 on 15 carries.
"It's something to build on. If we can take (penalties) out, we might score a few more touchdowns," Locker said. "I'm excited about what we did offensively, but the fun part for us is that get to go back and look at it. I think we left a lot out there."
While the Titans look to open 2-0 for the first time since last reaching the playoffs six years ago, the Cowboys will try to avoid dropping their first two for the first time since their last losing season - a 6-10 effort in 2010.
In Week 5 of that season, Romo threw for a then-career high 406 yards and three scores against Tennessee, but had two costly picks in the fourth quarter of a 34-27 home defeat.
The three-time Pro Bowler is trying to rebound from offseason back surgery and a rocky opener. He didn't appear comfortable throughout Sunday's game, going 23 of 37 for 281 yards with one touchdown and three interceptions in a 28-17 home loss to San Francisco.
''Tony will be fine,'' said tight end Jason Witten, limited to two catches for 14 yards. ''He'll bounce back. He's his own worst critic, and he's an elite quarterback.''
It certainly didn't help Romo that star receiver Dez Bryant missed much of the contest while battling dehydration, finishing with four catches for 55 yards.
The Cowboys will likely need to do plenty of scoring, as they didn't show a great deal of improvement defensively in the opener after allowing a league-high 415.3 yards per game in 2013. They gave up three early touchdowns while falling behind 28-3 before San Francisco seemed to ease up a bit in the second half.
Tennessee should provide Romo and the Cowboys with a stiff test defensively after picking off Alex Smith three times and limiting Jamaal Charles to 19 yards on seven carries Sunday in coordinator Ray Horton's new 3-4 scheme.
''It really doesn't mean anything if we don't make this a consistent thing,'' Whisenhunt said.
The Titans are looking at their options at linebacker after losing Zach Brown for the rest of the season due to a torn pectoral muscle. Zaviar Gooden could be the answer after replacing Brown in the opener.
This is the first meeting in Tennessee since the Cowboys' 45-14 victory in 2006.