Where the 49ers Will Be Challenged the Most in Week 3 vs. Cardinals

This area will be an issue for the 49ers against the Cardinals in Week 3.

Sep 20, 2026; Santa Clara, California, USA; San Francisco 49ers defensive tackle Gracen Halton (93) tackles Miami Dolphins running back De'Von Achane (28) in the fourth quarter at Levi's Stadium.c=. Mandatory Credit: Kyle Terada-Imagn Images | IMAGN IMAGES via Reuters Connect

Opening the season 3-0 is well within the 49ers’ grasp. 

They get to stay at home again and play another weak team. This time it’s their division rival, the Cardinals. It shouldn’t be too difficult for the 49ers to handle them.

Arizona hasn’t looked impressive early on this season. However, that doesn’t mean the 49ers should overlook them. In fact, the Cardinals can challenge the 49ers the most in one area.

It’s not specifically anything that the Cardinals have proven to do in two games this season, but it’s the potential of what they can do if they recognize the 49ers’ weakness.

That’s running the ball straight through the 49ers’ interior defensive line. It’s low-hanging fruit for the Cardinals to exploit that area. It’s been the weakest facet of the 49ers so far this year.

Now that C.J. West is on Injured Reserve, they’re trotting out a bunch of players who just joined the team. Osa Odighizuwa and rookie Gracen Halton are the only positively impactful players.

But the 49ers can’t have them out there on every snap. That is when the Cardinals will expose that area by running the ball with their top draft pick, Jeremiyah Love, and Tyler Allgeier. 

Sep 13, 2026; Inglewood, California, USA; Arizona Cardinals quarterback Jacoby Brissett (7) hands off to running back Jeremiyah Love (4) against the Los Angeles Chargers during the first quarter at SoFi Stadium. Mandatory Credit: Kiyoshi Mio-Imagn Images | IMAGN IMAGES via Reuters Connect

Arizona hasn’t featured Love much this season, which can mostly be attributed to the high ankle sprain he suffered in the first preseason game. The Cardinals don’t want to overwork him and aggravate it.

However, it’s been some time since he injured it. He should be at, if not close to, 100%, which should be enough for the Cardinals to use him more. There’s no better game for them to do it than this one.

They’re playing their NFC West rival on the road. No one will be giving them a shot at winning. They can pull a massive upset by riding the coattails of their prized No. 3 overall draft pick.

This can be Love’s breakout game, and if he does it against the 49ers, it’ll start to get people looking at the Cardinals a little differently. It’ll also cause panic with the 49ers.

Being unable to defend the run adequately against the Cardinals will scream to the NFL what their Achilles heel is. The worst part is there’s no fixing it through schematic changes.

They have no depth with all of the injuries. Free agency doesn’t provide any decent options either, which means they’ll need to look strongly at trades to make.

The issue with that is no one will want to make any trades for another few weeks. Arizona has a chance to lay out the blueprint for how to defeat the 49ers. They have the ability to do it.

San Francisco must do what they can to avoid that from happening.

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