More important than head-to-head records is the fact that the Titans can't afford to open the season 0-2 with the Detroit Lions coming to Nashville after that.
The Chargers aren't the darlings of the AFC West anymore, but they still pack a deadly punch on offense with Philip Rivers under center.
The last time these teams met, Rivers torched the secondary for over 300 passing yards and two touchdowns.
Here are five keys to the Titans getting a critical road win that is never easy on the West Coast.
It's being reported that Kenny Britt will see anywhere between 15 to 25 snaps in what will be his first action since early last season.
During that limited action, Britt will need to make some solid contributions to free up space for the other Titans receivers.
Jake Locker desperately needs a big target like Britt to help him continue his transition into an everyday starter in the NFL.
Britt probably doesn't have the fondest of memories of playing against the Chargers, as he injured his hamstring the last time these two teams met. The injury forced him to miss four games that season.
If anything, Britt's presence should help Chris Johnson get a little more space to work with in the backfield since the Chargers defense will want to focus on containing Britt.
Britt has the ability to take over games like many of the other star wide receivers in the NFL, but just having a modest output in limited action will still do wonders for this offense.
Even though Locker isn't technically a rookie, it's still fair to consider him one this season.
Big mistakes like the fumble inside his own 5-yard line was a prime example of some of the growing pains that Locker is going to suffer this season.
It didn't help that there was no run game to speak of, which led to Locker trying to force things that weren't there.
Locker simply can't do that against the Chargers. He has to be able to stick to the game plan and not try to make up double-digit deficits in one play.
As stated earlier, the return of Kenny Britt should help Locker out, knowing he has a big target to throw to.
It's also important that Locker doesn't fall too in love with his cannon for an arm. There's nothing wrong with throwing a little finesse into the equation every now and then.
The throw that Nate Washington was injured on was a throw that Locker probably could have taken a little off of. His cannon forced Washington to go up high for the ball, which in turn left him vulnerable to a nasty hit.
Overall, Locker played well against the Patriots, but avoiding the big mistakes should keep this game close to the end for the Titans.
Antonio Gates really burned the Titans back in 2010, and you can bet that he'll be a major part of the Chargers game plan this time around.
That means Akeem Ayers and the other Titans linebackers are going to have to play solid coverage to keep Gates from taking over this game.
Once again the Titans struggled with opposing tight ends in Week 1 as they gave up 12 receptions and 119 yards to Rob Gronkowski and Aaron Hernandez.
They also added two touchdowns to those monster numbers.
The Titans can't let that happen against the Chargers, or a similar fate will be handed down.
It's going to be a long day for the Titans secondary if Philip Rivers is given a lot of time to sit in the pocket. That's just what elite quarterbacks do. They pick you apart.
Despite only getting one sack on Tom Brady, the defensive line actually played pretty well to open the season. Some of that can be attributed to Kamerion Wimbley, who got the sack on Brady.
The Titans will not have the luxury of rushing the linebacker too often. It's just a bad idea when you've got an athletic specimen like Antonio Gates lining up against you.
For the Titans to get the pressure they need on Rivers, the defensive line is going to have to get solid pressure without blitzing too often.
It's really not rocket science. Quarterbacks have a hard time picking you apart if your defensive line is constantly in their grill. If the Titans can do that, then they'll have a great chance at ending this eight-game losing streak to the Chargers.
This one really is a no-brainer for the Titans. You have to be able to run the ball in the NFL to be a consistently successful team.
Offensive coordinator Chris Palmer really has to start mixing things up more with his running backs.
That might mean using a big back like Jamie Harper more. Harper seeks out contact, whereas Chris Johnson is just simply not that type of runner.
Changing the pace up with your running back personnel might be exactly what Johnson needs to jump start his 2012 season.
For whatever reason, Johnson looked even worse than he did at any point last season. Some of that is thanks to the offensive line not getting a good push, but Johnson has to figure out a way to scratch and claw for two or three yards on first down.
It's absolutely killing this offense's potential when they're not getting at least a couple yards on first down.
The field will open up so much more for Locker in the passing game if Johnson can even manage 50 yards on the ground.