What the Biggest Challenge Will be for the 49ers Against Indianapolis

If the 49ers aren't prepared for this against the Colts, then it will be difficult for them to emerge victorious.

Nov 30, 2025; Cleveland, Ohio, USA; Cleveland Browns running back Dylan Sampson (22) runs the ball during the second half against the San Francisco 49ers at Huntington Bank Field. Mandatory Credit: Ken Blaze-Imagn Images | Ken Blaze-Imagn Images

The Indianapolis Colts are currently riding a four-game losing streak. It makes their matchup perfect timing for the San Francisco 49ers.

However, the Colts still have facets to be worried about. Their defense is still a strong one and must not be downplayed despite players missing.

But there is another area where the 49ers will be challenged the most by the Colts. If they're not well-prepared for it, then they will struggle to emerge victorious.

The Colts pose the biggest challenge to the 49ers here

Houston Texans linebacker Azeez al-Shaair (0) attempts to tackle Indianapolis Colts running back Jonathan Taylor (28) on Sunday, Nov. 30, 2025, during a game at Lucas Oil Stadium in Indianapolis. | Christine Tannous/IndyStar / USA TODAY NETWORK via Imagn Images

It’s defending against stalwart running back Jonathan Taylor. He’s been stupendous for the Colts this season. For as terrific as Christian McCaffrey has been this year, Taylor has been better.

He’s the engine of their offense. The Colts’ offense will go as far as he does. Even with Phillip Rivers in the fold, he’s still a threat to wreak havoc against the 49ers’ defense. 

It’s largely because his strengths are a weakness for the 49ers’ defense. Robert Saleh loves to run nickel personnel nearly 80 percent of the time, the highest of all defenses. 

Taylor is averaging 5.8 yards per carry against nickel personnel this season, the fourth-most among running backs with at least 50 carries. He has also scored a league-high nine rushing touchdowns against nickel, four more than the next closest running back.

The 49ers allow 4.7 yards per carry out of nickel formation, which is slightly below the league average. Taylor is bound to gash them in this look.

[US, Mexico & Canada customers only] Nov 9, 2025; Berlin, GERMANY; Indianapolis Colts running back Jonathan Taylor (28) celebrates his touchdown in overtime against the Atlanta Falcons during the Berlin Game at Olympic Stadium. Mandatory Credit: Lisi Niesner/Reuters via Imagn Images | Lisi Niesner/Reuters via Imagn Images

And the Colts will most likely utilize him in the shotgun to do so. Taylor has taken 52.2 percent of his carries in shotgun formation this season, the fourth-highest rate among running backs with at least 75 carries.

He leads the league with 684 rushing yards on shotgun carries (4.8 yards per carry), 214 more yards than the next closest player, and has scored a position-leading six touchdowns on those runs. 

The 49ers' defense has allowed running backs to average 5.3 yards per carry on shotgun runs, the second-most in the NFL, along with a 48.9 percent success rate, also the second-highest in the league.

If Taylor gets going in this game, it will be difficult to win. They have to be able to limit him at the very least to force Rivers to throw. That’s the 49ers’ best chance to win.

It’s by making Rivers throw as much as possible. Otherwise, the 49ers’ offense will be expected to score over 30 points for a chance to win. 

Follow Jose on X (Twitter) @JS3sanchezz to interact with him and subscribe to his YouTube Channel here for more 49ers content.

---