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This week's edition of the regularly-scheduled "Monday Night Football" game sees the first-place Buffalo Bills head to Arizona to take on the San Francisco 49ers. 

The Bills enter this contest at 8-3, just a half-game ahead of the Dolphins for the division lead. They need a victory to keep pace with the Cleveland Browns in the race for the No. 3 seed in the AFC, and to keep a bit of distance between themselves and Miami in the AFC East. 

San Francisco, meanwhile, got some help on Sunday when it comes to keeping its faint playoff hopes alive. Not only did the Giants take down the Seahawks, but the Rams knocked off the Cardinals, dropping Arizona's record to 6-6. If the Niners can score a "home" victory over the Bills on Monday night, they will match Arizona and Minnesota's win-loss marks, making things much more interesting down the stretch of the season. 

COVID-19 precautions in Santa Clara County forced the 49ers to move this "home" game to the Cardinals' home stadium in Glendale, Arizona (there will also be a second Monday game, with Washington taking on the Steelers at 5 p.m., and you can check out our preview and how to watch that game here).

Let's break down the Bills-49ers matchup. 

How to watch

Date: Monday, Nov. 30 | Time: 8:15 p.m. ET
Location: State Farm Stadium (Glendale, Arizona)
TV: ESPN | Stream: fuboTV (try for free)
Follow: CBS Sports App

When the Bills have the ball

The Bills are coming off a nice win against the Chargers, coming back strong from their bye week following a heartbreaking loss to the Cardinals back in Week 10. Josh Allen seems to have gotten over his midseason lull, but that will be tested against an excellent San Francisco defense that remains among the best in the league even despite hemorrhaging talent throughout the year. 

The Niners entered the week ranked ninth in Football Outsiders' defensive DVOA despite none of K'Waun Williams, Richard Sherman, Nick Bosa, Solomon Thomas, or Dee Ford playing more than 28 percent of the team's defensive snaps, and the D-linemen playing far less than that. The 49ers have also had each of Dre Greenlaw, Emmanuel Moseley, Jason Verrett, Dion Jordan, Jaquiski Tartt, and Kwon Alexander miss at least two games. And again, this team ranks sixth in yards, 11th in points, and ninth in DVOA, with borderline top-10 units against both the run and the pass. Robert Saleh might be an actual wizard.

The big thing to watch on this side of the ball is how the Niners elect to align their corners against Buffalo's wide receivers. Sherman and Verrett will presumably be the starters on the perimeter as they were last week, with Jamar Taylor and/or one of the safeties picking up work in the slot. 

If John Brown were healthy, then simply playing sides with Sherman and Verrett would make sense, with one of them handling Brown and the other Stefon Diggs depending on where they line up. Might Sherman shadow Diggs with Brown out, though? Gabriel Davis looks like a solid player, but he certainly hasn't earned the same respect from defenses as either Diggs or Brown just yet. If San Francisco does elect to shadow, the 49ers could end up getting burned by Beasley in the slot. Williams is their usual slot corner, and he's a good one, but his high-ankle sprain is likely to keep him out a bit longer. Beasley torched the Cardinals' weak slot defense a few weeks ago, and could do the same here if Taylor isn't up to the task. 

From Buffalo's perspective, the Bills absolutely need to devote as many resources as they can to making sure Allen is well-protected. The San Francisco pass rush is still strong even without so many of their top dogs, and Allen has a tendency to let early-game pressure rattle him for entire games. If they can get him to get the ball out quickly on the first couple drives for some easy completions, that'd let him settle into a nice rhythm. One way Buffalo has been doing that has been by going empty, inviting a blitz, and checking to a quick smoke screen to the perimeter. Watch out for that early in the game if the Niners show a blitz look. 

The Bills have been one of the most pass-oriented teams in the league for much of the season, really only focusing on the running game when Allen has shown signs of not being up to the task on that particular day. Zack Moss seemed to have leapfrogged Devin Singletary in the pecking order before the bye, but Singletary jumped back in front last week. Most likely, they'll split the work and ride the hot hand if there is one. Given San Francisco's stout run D, the two backs' biggest contributions figure to come in the pass game anyway. 

When the 49ers have the ball

The 49ers are still not fully healthy on offense, but they're getting closer. Raheem Mostert has returned from injury. So has Deebo Samuel. Jerick McKinnon and Jeff Wilson are around to contribute behind Mostert in the backfield and Jordan Reed is no longer injured. (Though is is dealing with an illness.) Brandon Aiyuk was activated off the COVID-19 list earlier this week. They're still down Jimmy Garoppolo, George Kittle, and Tevin Coleman, but that's a far cry from the monstrous list of players they were missing earlier in the season. 

Nick Mullens has been extremely up-and-down leading this offense over the past few weeks, to put it kindly. He has proven to be something like a replacement-level quarterback during his time under center, and we shouldn't necessarily expect that to change any time soon -- if ever. That said, there are reasons to think he can find some degree of success in this matchup. 

First of all, the Buffalo defense simply has not been as good this year as it has during the previous years under Sean McDermott. The Bills entered Week 13 ranked 21st in yards allowed and 18th in points allowed, as well as just 16th in Football Outsiders' DVOA. The Bills are the 15th-ranked unit against the pass and 22nd against the run. They have specifically backslid against the pass, going from ranking second and sixth in DVOA over the past two years to just a borderline average unit this year. They've allowed a 97.7 passer rating on play-action throws, which the 49ers run more than almost any other team. 

The 49ers' perimeter playmakers are also not really the type of guys who can be shadow-covered by Tre'Davious White in the way you'd typically expect shadow coverage. Samuel and Aiyuk line up all over the formation, including occasionally in the backfield. They are constantly in motion, whether receive (or be faked) a jet sweep or simply to allow the Niners to identify coverage. They get thrown smoke screens, bubble screens, and jet flips. They're heavily involved in the run game on jet sweeps, end-arounds, and even toss plays. It's not like they're lining up outside and running one-on-one routes every snap, or even on all that regular a basis. If Kittle were healthy it might make some sense to use White on him, Darrelle Revis-style, but he's not. So it'll be interesting to see how Buffalo elects to play this one. 

The 49ers, though, prefer to base their offense around the best-designed run game in the NFL. Even without Kittle (the best blocking tight end in the league), the Niners are still able to run the ball at an efficient clip. Mostert, upon return, has resumed clear lead back duties, and we should expect that to continue here. The 49ers love to get him out in open space by using misdirection and fakes, and he is remarkably fast once he puts his foot in the ground, cuts upfield, and hits the jets. If the Bills don't close down those rushing lanes immediately once he cuts, he could gash them for huge gains. 

It's imperative against the 49ers to not bite on all the fakes and misdirection action ... but it's also imperative to contain the jet sweeps and end-arounds and leak plays. Kyle Shanahan knows the rules of opposing defenses and how to put defenders in conflict, and he does it with more consistency than any non-Andy Reid play-caller in the league. He's even able to do it while working short-handed and with a backup quarterback, and it won't be surprising if the 49ers manage to put some crooked numbers on the board in this spot. 

Prediction: 49ers 24, Bills 23