With their season in balance and rapidly fading, the San Francisco 49ers are staying on the road for a matchup with the Buffalo Bills in cold temperatures on Sunday night, with kickoff slated for 5:20 p.m.

The 49ers are coming off their worst loss of the year, dropping a 38-10 game to the Green Bay Packers to fall to 5-6 on the season, but they still remain one game out of the divisional race.

Now, they face a Buffalo team that has been one of the hottest in football this season, standing at 9-2, having won their last six games. In fact, they’ve scored at least 30 points in their last five games, and they have a chance to clinch the AFC East this weekend.

San Francisco comes into this game down five potential starters as defensive end Nick Bosa, left tackle Trent Williams, cornerback Deommodore Lenoir, guard Aaron Banks, and defensive tackle Jordan Elliott were all ruled out on Friday.

What’s the formula to success for the 49ers against Buffalo on Sunday?

Run the ball

The Bills have been one of the more dominant teams in the NFL this season, jumping out to leads early and forcing teams to play from behind.

As a result, they’ve allowed only 119.1 rushing yards per game, good for 14th in the NFL. However, when you look at the average yards per carry, it’s a completely different story.

Buffalo allows 4.9 yards per attempt on the ground, good for 29th in the NFL, providing San Francisco with a potential avenue for success on Sunday.

Now, the Bills do get a huge boost back as star linebacker Matt Milano was activated off Injured Reserve and is expected to play, but San Francisco needs to establish themselves on the ground or capitalize from the heavier boxes with success in the air.

Christian McCaffrey hasn’t started off the year well. Through three games, he has just 139 rushing yards and is averaging 3.5 yards per carry, leaving some bread on the bone on some of his rushes.

This could be the get-back game for McCaffrey, who has been the bonafide No. 1 back upon his return, with backups Jordan Mason and Isaac Guerendo combining for just seven carries over the last three games.

It may be tough to run the football to the coveted left side, as the 49ers are missing both Trent Williams and Aaron Banks. But, they have got to get the run game going to slow this one down and not let Buffalo get out to that early lead.

Win the turnover battle

Winning the turnover battle is crucial in every game, but it’s extremely important on Sunday because 1) it’s actually realistic and 2) the 49ers need to slow down the Bills’ offense.

San Francisco is 4-0 this year when they’ve won the turnover battle. On the flip side, they’re 0-2 when the turnover battle is tied and 1-4 when they’ve had a negative takeaway differential.

Buffalo has been elite at forcing turnovers, which will be a big factor to watch on Sunday. Not only have they forced at least one in every game, but they also rank fourth in the NFL with 1.9 takeaways per game.

On the flip side, they’re one of the best teams when it comes to protecting the football, ranking second in the NFL with just 0.6 turnovers per game.

But, quarterback Josh Allen has thrown at least one interception in each of the last four games. Albeit, Buffalo has won all of those games, however; there’s an avenue of opportunity there for San Francisco.

The 49ers have really struggled with the turnovers this year, as they rank 24th in the NFL with 1.5 giveaways per game. They are, however, one of the best at forcing turnovers, ranking eighth in the league with 1.5 takeaways per game.

Brock Purdy will need to take care of the football behind a makeshift offensive line, but the 49ers defense will also need to come to life in this one.

Red Zone

Perhaps the biggest key in this one to slow the game down will be red zone play on both sides.

It’s been well-documented that the 49ers are one of the worst teams in the red zone this year after being the best in the NFL in 2023. They rank 25th in the NFL, converting just 50 percent of their drives to touchdowns, while being even worse defensively, ranking 27th by allowing 67.6 percent of opponent drives to result in touchdowns.

If you’re as good of a football team as Buffalo is, you’re probably pretty good in the red zone. And the numbers back that up.

The Bills have converted 63.8 percent of their red zone drives to touchdowns (6th in the NFL), and get inside the opponent’s 20-yard line at the highest rate in the NFL with 4.3 drives per game.

Defensively, they’ve been stout, allowing just 51.3 percent of opponent red zone drives to end in touchdowns, ranking 10th in the NFL.

If the 49ers want a chance here, they’ll need to slow the game down, and a great way to do that is winning in the red zone. The numbers are against them here, but that’s what’ll need to happen for them to have a chance on Sunday night.