One player who might be asked to step up is quarterback Brock Purdy. Despite leading the NFL with 550 passing yards, Purdy has only thrown one touchdown compared to one interception over two games.
Hall of Fame quarterback Steve Young believes Purdy already excels in one key area—processing what's happening on the football field.
"He is top of the league in doing that," Young told Suzy Shuster and Amy Trask on the "What the Football" podcast.
Purdy may not be the biggest or strongest passer in the league, but Young feels the 49ers' third-year quarterback compensates for that with his sharp football IQ and ability to read defenses.
With McCaffrey and Samuel out, Purdy will likely have to elevate his play even further to help the 49ers weather the loss of two of their biggest playmakers.
Young recognizes that Purdy won't suddenly transform into a different type of quarterback. He's not going to become a big-time scrambler or a dynamic offensive weapon. That's not what he is.
"If they're going to stay with the same plan, then the demand for Brock is even greater," Young said. "He has to be even more honed on his efficiency to find players that aren't necessarily [at] the top of the game like Deebo, the top of the game like CMC. And now I've got to figure out how to get the ball to them, have them get open."
Young believes this stretch could push Purdy to expand his skill set.
"Inevitably ... he's going to have to do more," Young continued. "He's going to have to move around more. He's going to have to put himself at risk more, and he's going to have to do things that aren't necessarily his strong suit, and that might provide great things in the future for when they get the Super Bowl this year and have to face Patrick Mahomes or face Lamar Jackson."
Young also pointed out a challenge the 49ers have faced in recent years when going up against elite quarterbacks. Despite being a talented team, they haven't always fared well in those matchups.
"The thing about the 49ers, when they face Joe Burrow, Lamar Jackson, Patrick Mahomes, any big, strong, prototypical quarterback today, they lose," Young said. "So getting their guy more like that, and under duress, like with injuries, might be a good thing."