The San Francisco 49ers are set to travel to Philadelphia to face the Eagles in their second-straight road game to open up the 2021 NFL season.

The Niners are 3.5-point road favorites against a Philadelphia team that showed big-play ability on offense and pocket collapsing ability on defense.

Here are seven storylines to follow in this intriguing Week 2 matchup.

1. Can Eagles handle success?

Philadelphia Eagles defensive tackle Javon Hargrave

Philadelphia Eagles defensive tackle Javon Hargrave (97) celebrates his sack of Atlanta Falcons quarterback Matt Ryan.

A team that entered last Sunday with low expectations is suddenly the talk of the NFL and now Philadelphia has to do it again in front of the home crowd.

2. 49ers RB Situation without Raheem Mostert

San Francisco 49ers running back Elijah Mitchell (25) runs by Detroit Lions defensive back Tracy Walker III (21) Sunday, Sept. 12, 2021 at Ford Field.
Lions 49ers

During the 2021 NFL draft, the 49ers selected Trey Sermon in the third round and Elijah Mitchell in Round 6, and both players will see time with Raheem Mostert out with a season-ending knee injury.

The 5-foot-10, 200-pound Mitchell logged 19 carries for 104 yards and a touchdown in Sunday’s win at Detroit.

3. 49ers injury woes continue

Mandatory Credit: Joe Camporeale-USA TODAY Sports

Mostert is out, along with losing cornerback Jason Verrett to a season-ending torn ACL vs. Detroit. The team instead signed Dre Kirkpatrick, who started 11 games at corner for the Cardinals in 2020.

4. 49ers two QB situation

Mandatory Credit: Kyle Terada-USA TODAY Sports

Philadelphia knows what it’s like to have an apparent quarterback controversy and this week they’ll prepare to face an incumbent starter in Jimmy Garoppolo and a fast-rising rookie in Trey Lance.

In Sunday’s win at Detroit, Garoppolo threw for 314 yards and one touchdown while Lance took just four snaps, which included a 5-yard TD pass on his only throw of the day.

Lance only saw the field for four snaps because the 49ers didn’t need him to beat the Lions and he also missed a week of practice with a small finger fracture.

5. Revenge game?

(AP Photo/Jed Jacobsohn)

The 0-2-1 Eagles badly needed a win last October and promptly traveled to Santa Clara, California to hand the 49ers an upset loss at home. Carson Wentz is gone, and that injury-riddled San Francisco team is now healthier and looking for some revenge.