The 49ers are widely perceived as the more talented franchise, but the fierce rivalry ensures that the outcome is always unpredictable between these two teams, which was made perfectly clear Nov. 12.
When these teams met in Week 10, the Rams played a tough match on the road against a superior opponent and managed to send the game into overtime. The overtime battle was a roller coaster, as both teams had opportunities to win the game and came up short. In the end, the game ended in a tie, making it one of the most unique and memorable matchups of the 2012 NFL season.
Naturally, the lack of closure from the last game has fans eager for the rematch, and it likely won't disappoint.
The Rams will have the home-field advantage this time around, but defeating a juggernaut 49ers team is always a difficult task.
For that to happen, here are seven keys the Rams must focus on.
1. Strike Early
The Rams have been solid at producing points early on in games. Even against New England in their worst game of the season by far, the Rams were still able to jump ahead of the Patriots with a 7-0 lead in the first quarter.
While early leads haven't always paid off for the Rams this season, it's important that they come out firing in the opening quarter and earn a two-score lead in the early goings. This will give them early momentum and force the 49ers to play catch-up for the remainder of the game.
In both of the 49ers' losses this season, they allowed the opposing team to score the first touchdown of the game. Their defense can make it difficult to rally a comeback, making early points vital for St. Louis.
2. Repeat Performance for Sam Bradford
When these teams met in Week 10, Bradford threw for 275 yards and a pair of touchdowns in what was one of his better games this season.
Bradford is a major reason why the Rams were in that game until the bitter end, and his play will be a major factor this Sunday.
Bradford had a lousy game against the New York Jets during the team's last home game, but he has been more consistent as of late. He has exceeded 200 yards and thrown a touchdown in five of his last six games.
If the Rams want to win, they cannot afford Bradford falling into a rut.
3. Danny Amendola's Health
Danny Amendola was expected to miss last week's action against the Arizona Cardinals due to injury. Surprisingly, he remained active for the game and contributed a key 38-yard catch, though that was his only reception of the game.
This week, Amendola is once again missing practice due to his foot injury (according to the St. Louis Rams Twitter account):
WR Danny Amendola (foot), C Scott Wells (knee), LB Mario Haggan (elbow) and DE Robert Quinn (concussion) did not participate.— St. Louis Rams (@STLouisRams) November 29, 2012
Amendola contributed 11 grabs for 102 yards against San Francisco three weeks ago, and his absence could hinder the offensive efforts.
Then again, the team was without Chris Givens in Week 10. Givens has emerged as an extremely valuable playmaker as of late, and his availability will help out if Amendola is not available.
4. Colin Kaepernick's Consistency
Colin Kaerpernick has started the last two games for San Francisco and has been very effective, with a combined 474 yards and four touchdowns in those two games.
Kaepernick appeared in the Week 10 game against the Rams, and his mobility gave them fits, as he rushed for 66 yards and a touchdown.
Kaepernick has been a very solid starter for the 49ers and has recorded wins in both his starts, but the second-year player is bound to commit mental errors at some point, and that would certainly help the Rams put this game away.
Jeff Fisher needs to mess with Kaepernick's head by throwing a variety of defensive formations his way, making the packages harder to identify.
5. The Quinn Factor
Robert Quinn is also on the injury report this week with a concussion, and his status for Sunday's game is still uncertain.
The Rams will certainly miss his pass rush, but his run defense will not be missed. During the last game between these teams, many of Colin Kaepernick's 66 rushing yards came on Quinn's side of the field.
If Quinn is out, the Rams need to start the best run-defending end left on their roster to contain Kaepernick.
If Quinn is good to go, they need to be sure he's ready to handle the run game this time around. If not, they may want to limit him to passing situations only.
6. Remain Disciplined
In Week 10, the Rams outplayed the 49ers and should have walked away with a very promising road victory. Instead, a wave of mental errors and blatant incompetence cost them the game.
There's no excuse for a fourth-year receiver not know where to line up, and there's certainly no excuse for a delay of game penalty during a game-winning field.
The Rams lost the opportunity to win not because of poor play, but because of pure nonsense.
Discipline is required on Sunday if the Rams want to beat a team of San Francisco's caliber.
7. Offense, Offense and More Offense
The Achilles' heel of the 2012 Rams has been the inconsistency of their offense, which has been non-existent at times this season.
In basically every loss this season, the offense has been the primary culprit. Either it can't score with the game on the line, or it enters a rudderless state of total discouragement and loses all rhythm.
In several of the games this season, such as the New England nightmare, it appears the offense is completely overwhelmed and not even trying to compete. It's as if the unit gives up as a whole if the team falls behind by more than two or more scores.
In this case, whether the Rams are winning or losing, it would be nice to see the offense compete and produce for four quarters.
Don't let the 49ers breathe easy at any point, even if they hold a two-score lead for the entire game.