The Titans are coming off a disappointing loss to the Cleveland Browns but are still in great position to take control of the AFC South with a 1-1 record and no teams in the division at 2-0.
As for the Colts, they're already in desperation mode. They can't afford to go to 0-3, even in a division that virtually every expert has them winning.
Offensive Game Plan
Both teams enter this game with injuries at important positions, but the Colts may have the worst of it. They're most banged up in the secondary, with Darius Butler, Greg Toler and Vontae Davis all dealing with injuries.
Butler was unable to practice on Thursday, per Jason Wolf of the Tennessean.
This is a good sign for a Titans passing attack that still has a lot of upside despite a rough outing against the Browns. Much of that struggle was due to Marcus Mariota not having time to throw and wait for his receivers to run their routes.
The Titans need to capitalize on the Colts being weak in this area. Mariota has already shown that he can light up secondaries that aren't at full strength.
Tight end Delanie Walker is expected to be back in action after suffering a hand injury in Week 1. He is so vital in both production and his on-field leadership.
This Colts defense is vulnerable and should be much easier to move the ball on than the Browns were the previous week.
Dorial Green-Beckham needs a bigger role in this offense. The wide receiver was removed from organized football for nearly a year coming into the regular season, but he seems to be gradually becoming more comfortable. His size will be tough for the Colts' depleted secondary to defend.
There's excitement and optimism from Titans general manager Ruston Webster on Green-Beckham's potential, via Paul Kuharsky of ESPN.com:
Good teams figure out ways to use their weapons effectively. Green-Beckham is one of those weapons that needs to be unleashed.
The Titans also seemed to find something that worked with Dexter McCluster in the running game. If McCluster can follow that up with another solid contribution, it will enhance the team's chance to win.
It's obvious that the Titans rushing attack will be very hard to predict from week to week.
Defensive Game Plan
The Titans are still up for a tough challenge facing Andrew Luck. Despite his early-season struggles, Luck is still quickly ascending into one of the best quarterbacks in the league. He is the future of the position, and the Titans cannot let him get into a groove. Extending busted plays is how he beats a lot of teams. He's fully capable of leading the Colts to a win in shootout style.
Titans defensive coach Dick LeBeau compared Luck to another great quarterback, via Jim Wyatt of TitansOnline.com:
LeBeau said Colts QB Andrew Luck reminds him of Steelers QB Ben Roethlisberger with his ability stay on feet and deliver the ball— Jim Wyatt (@jwyattsports) September 24, 2015
It won't be as simple as just putting pressure on Luck. He's savvy enough to make adjustments and still burn you. This game has to be one-dimensional, forcing Luck to rely solely on his arm. That means shutting down Frank Gore.
Gore has done some great things in his career, but the 32-year-old is on the back end of his time in the NFL. Keeping him from gaining large chunks of yardage of first and second down will stack the odds in the favor of the Titans secondary.
Sloppy tackling has plagued the Titans occasionally over the first two weeks. Doug Martin had some success in Week 1, and so did Isaiah Crowell. Gore, even at his older age, is better than both of them. He will take full advantage of sloppy tackling by the Titans. Cleaning up that area on defense is critical.
There's another aging veteran whom the Titans painfully know all too well, and that player is Andre Johnson. The 34-year-old has clearly lost a step or two, but the Titans cannot let Johnson beat them. He's frankly the Colts' only legitimate receiving option with T.Y. Hilton not 100 percent. Contain Johnson, and the Titans will be in good shape to keep the Colts from running up the score.
Forget about the Colts being 0-2. They're still better than many teams in the AFC and still the team to beat in the AFC South. The Titans can't let this opportunity slip away.
This entire team realizes how important this game is if the Titans want to back up the notion that they're very different from last year's 2-14 team.
A loss here in the home opener against a depleted Colts team will leave everyone wondering if this is still the same disappointing team.
The tough sledding the Titans have experienced in recent years will finally come to an end. They're catching the Colts at just the right time with injuries, a short week and a crowd that will be louder than it's probably been in several years.
There will be a moment in this game when the Titans will reach a major fork in the road. They'll have to make a defensive stop against Luck to preserve this win. Old Titans teams would fold here and lose a golden opportunity to take control of the division. This Titans team won't do that.
They'll make a major defensive stop and hold on tight to win 28-24.