If you’re trying to stop the 49ers’ offense, you have to start with McCaffrey, who deserves some legitimate MVP chatter. That’s how good he has been and how much he has meant to the 49ers’ offense.

In 11 games this season, McCaffrey already has 1,328 scrimmage yards and 16 touchdowns. He’s an incredible runner but you also have to account for him as a receiver. And he’s not just some finesse player either. McCaffrey is great after contact, averaging 2.0 yards after contact per attempt this season. First, you gotta catch him, then you’ve gotta tackle him.

“You’ve got to put bodies around him,” Eagles defensive coordinator Sean Desai said. “Have to get different looks, affect his route progression from different angles and put different matchups on him because they do a great job of creating matchups there. So, we’ve got to be able to have multiple different ways and different angles at which we want to cover him and leverage them.”

In addition to McCaffrey, the 49ers also have one of the best tight ends in the NFL in Kittle, who has 46 catches for 667 yards and 5 touchdowns. The Eagles have struggled against tight ends at times this season and they won’t be able to give Kittle the same type of attention they gave Travis Kelce a couple weeks ago because the 49ers have too many offensive weapons.

This season, the Eagles have given up 55 catches for 520 yards and 6 touchdowns to opposing tight ends. They did a nice job on Dalton Kincaid last week but before the bye, Cowboys TE Jake Ferguson gave them fits.

On top of all that, it sounds like LB Zach Cunningham (hamstring) won’t be able to play in this game. That means Nicholas Morrow and Christian Elliss will likely start.

Eagles cornerbacks vs. Deebo Samuel, Brandon Aiyuk

After last season, when the 49ers were in full sour grapes mode, Deebo Samuel called Eagles cornerback James Bradberry “trash.” And when given the chance to walk that back this week, Samuel said he didn’t regret any of his comments.

Bradberry, of course, is not trash. He might not be the best cornerback in the NFL but he was a second-team All-Pro last year and is coming off what was probably his best game in 2023 against the Bills. For what it’s worth, Bradberry took the high road this week when asked about Samuel’s comments.

The 49ers do have a strong 1-2 punch with Aiyuk and Samuel, who are third and fourth in receptions for that club this year. Aiyuk has 45 catches for 881 yards and 5 touchdowns, while Samuel has 34/474/1 this season in nine games.

Last week against Stefon Diggs and the Bills, the Eagles were unpredictable with Darius Slay traveling with Diggs at times and even into the slot. It would make some sense for Slay to stick with the speedier Aiyuk in this game, which could give us all the Samuel-Bradberry matchup we want to see.

Haason Reddick vs. Colton McKivitz

The 49ers have a pretty good offensive line and they’ve allowed just 21 sacks all season, which ranks tied for fourth-fewest in the NFL. Left tackle Trent Williams is  35 now but is still playing at an incredibly high level. And since K’Von Wallace is no longer here, he might actually make it through the entire game without getting in a fight.

If you’re looking for a matchup that is in the Eagles’ favor, it’s definitely Reddick against the 49ers’ right tackle McKivitz. That is, unless of course, the 49ers decided to block Reddick with a backup tight end again.

Reddick, 29, has 8 1/2 sacks in 11 games this season and has had another couple taken from him on intentional grounding calls. While Josh Sweat has probably been the Eagles’ most consistent edge rusher this season, Sweat will have to deal with Williams in this game.

Meanwhile, McKivitz is a former fifth-round pick who is in his first season as a full-time starter. He has given up a team-high five sacks, 3, QB hits and 27 total pressures, according to ProFootballFocus. So if there’s a weak spot on the line, that’s it and Reddick could have a big performance. And it also really extends to the entire right side of the line. Right guard Spencer Burford hasn’t been that solid either.

Lane Johnson vs. Nick Bosa

The Eagles had to play against the Bills without Lane Johnson, who was a late scratch with a groin injury. He attempted to warm up and test out his groin before that game but couldn’t go. While Jack Driscoll was able to play pretty well in that game, getting Johnson back for this one is a big deal. Bosa is the reigning Defensive Player of the Year after an 18 1/2-sack season in 2022. In 2023, he has 8 sacks and 29 QB hits through 11 games. He’s still the best player on that defensive line but there are other pieces to worry about.

Our old friend Javon Hargrave switched sides this offseason and has continued to rush the passer at a high level with the 49ers. Hargrave is second on the team with 6 sacks. And then the 49ers still have Arik Armstead and they added Chase Young at the trade deadline. The 49ers have 33 sacks as a team this year.

D’Andre Swift vs. 49ers run defense

The last time these two teams played the Eagles had 148 rushing yards but in that one the Eagles were able to build an early lead and kill clock in the second half. But even entering that game, the Eagles felt like they would have the ability to run against the 49ers.

Swift has clearly been the Eagles’ best running back all season but even Kenny Gainwell and Boston Scott chipped in last week against the Bills. Swift is just 29 scrimmage yards away from 1,000 on the season and he’s been pretty good the last two weeks, rushing for 76 yards against the Chiefs and 80 yards against the Bills. He’s also averaged 6.0 yards per carry over the last two.

The 49ers have the No. 2 run defense in the NFL, giving up just 82 yards per game. But the 49ers are 10th in the NFL in yards per attempt allowed.

Jalen Hurts vs. 49ers takeaway defense

Hurts is the favorite to win the league MVP award in 2023 and he’s been playing well, especially in seconds halves of games to lead the Eagles to wins. But he has turned the football over a little more than we’re used to seeing. Through 11 games, Hurts has already thrown a career-high in interceptions with 10 and he’s also lost 6 fumbles. His interception percentage of 2.8% ranks 8th in the NFL. That’s not awful but it’s not great either.

And in a game between two really talented teams, turnovers could be a big deal. Especially because this 49ers defense is particularly opportunistic. They’re tied for second in the NFL in total takeaways with 21 and they’re first in the NFL with 15 interceptions.

The 49ers’ leaders in interceptions this season are Fred Warner and Talanoa Hufanga with three apiece. But Hufanga suffered a torn ACL in Week 11 and is out for the season.