The Buffalo Bills will visit a bit of an unfamiliar foe in a very familiar venue on Monday Night Football in Week 13.

Rounding out the NFL’s slate, the Bills (8-3) face the San Francisco 49ers (5-6) in Arizona. Considering it’s another NFC opponent we don’t often see, let’s get all the details we can rounded up ahead of this one.

To find out more about the 49ers ahead of Monday, we stepped behind enemy lines with Kyle Madson, managing editor for our friends over at Niners Wire, to learn more:

The 49ers defense has stepped up with the ton of injuries they’ve endured this season. Who’s been the most impressive in doing so?

Two players have really stood out — defensive end Kerry Hyder and cornerback Jason Verrett. Hyder was a late acquisition in free agency and got pushed into a starting role when Nick Bosa went down with a torn ACL early in Week 2. He’s responded by leading the team in sacks and playing really well against the run. Verrett is finally healthy after playing only six games the last four years. He was a Pro Bowler his lone healthy season in 2015 and he’s playing like one again this year. San Francisco has been dealing with a slew of injuries in the secondary, but their pass defense has been strong in large part because of Verrett’s play.

The 49ers rushing attack, is that what the Bills are going to have to focus on shutting down in Kyle Shanahan’s offense?

With Nick Mullens playing quarterback, yes. Jimmy Garoppolo isn’t awesome, but he’s a bigger threat throwing the ball than Mullens is. RB Raheem Mostert is a threat to go the distance every time he touches the ball, but the more dangerous aspect of their run game is WR Deebo Samuel in jet motion. Technically those go as passes because Mullens does a little forward touch pass to Samuel, but it’s ostensibly a run play. Run plays out of that motion forces defenses to respect it pre-snap and it opens holes elsewhere when linebackers and safeties start cheating to stop it. Shutting the run game down and forcing Mullens to throw under pressure will be key for the Bills’ defense. I expect Leslie Frazier to dial up a ton of blitzes Monday.

Only five games for Deebo Samuel this year. Even with Nick Mullens under center, is the offense much better with Samuel and Brandon Aiyuk are healthy despite perhaps the Niners’ run-first approach at times?

Absolutely, because of what I described in the previous question. Aiyuk really broke out in Week 7 though which was the week Samuel hurt his hamstring. Since then the rookie WR has been excellent. The field-stretching element he offers is a perfect complement for a player like Samuel who’s most effective near the line of scrimmage. It remains to be seen just how good they can be together since they haven’t gotten a ton of snaps, but they’re both explosive playmakers whose styles mesh really well. If the run game gets rolling enough that the Bills’ pressure gets dialed back, Mullens might be able to do some damage with those two WRs.

This whole Arizona thing. The 49ers organization seems a little pissed about it. Do fans feel the same? Can’t imagine the Bills playing home games at Gillette Stadium or MetLife, either. Must be weird?

It’s a little strange. Fans are more concerned about the potential impact it could have on the team’s playoff chances than anything. Nobody was allowed to watch games at Levi’s Stadium anyway, so that’s not a problem. But the 49ers need to be close to perfect down the stretch to steal a playoff spot. The entire club getting uprooted on short notice to spend at least a month away from home will make that difficult though. Plus there are a ton of human issues players and personnel are dealing with that make it hard to be mad at the football aspect. It’s a weird situation that feels like people will have harder feelings about once we see how the team plays down the stretch.

Prediction. Who wins and why?

The fact the line on this game has shifted to 49ers -1 is absolutely wild. The Bills are really good, they’re more talented than this version of the 49ers, and they’re too well-coached to overlook a San Francisco team that just punched the Rams in the mouth. I think the 49ers stay close for awhile, but eventually the Bills get a lead and their defense can tee off on a quarterback that struggles against pressure. If San Francisco can force a couple turnovers they’ll have a chance, but even an average game from Josh Allen should be plenty for Buffalo to walk away from Levi- er, State Farm Stadium, with a victory. Bills 31, 49ers 13

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