SANTA CLARA – Hosting a Sunday night game is a perk best traced to the 49ers' Super Bowl campaign two years ago.

And it sure seems that long ago since they actually won a game at home.

After winning the 2019 season's NFC Championship Game, the 49ers have won only once on their home field – last Oct. 18 against the Los Angeles Rams on "Sunday Night Football."

The 49ers were decked out in all-white throwback jerseys that game. Now comes another throwback-jersey (red) and another chance at a home win on the Sunday night stage, where the 49ers (2-3) host the Indianapolis Colts (2-4).

"That's what you live for as a football player, to be on prime time when the whole world is watching you," right tackle Mike McGlinchey said.

The 49ers are 23-32 in regular-season action since moving into Levi's Stadium. That's bad – and familiar.

They opened 24-30-1 at their previous home of Candlestick Park, before their Super Bowl-winning dynasty took root there.

Here are five areas the 49ers must succeed in to shed a three-game losing streak after last weekend's bye:

1. SPOTLIGHT ON GAROPPOLO

Jimmy Garoppolo engineered a last-minute, go-ahead touchdown drive the last time a prime-time, national audience saw the 49ers. Then the defense surrendered that lead in 37 seconds for a home loss to Green Bay on Sept. 26.

The 49ers need Garoppolo's grit, again. He is 7-2 all-time under the lights, the only other loss coming in overtime fashion two years ago to the Seattle Seahawks.

Garoppolo missed the past 1 ½ games with a right-calf injury. So, no, he won't be running 16 times like Trey Lance did in his starting debut last game, a 17-10 loss at Arizona on Nov. 7.

Rather, Garoppolo must be prepared to win without relying so heavily on a play-action attack, mainly because the 49ers' running backs aren't as reliable as in past seasons.

With the Colts' safety situation impacted by Julian Blackmon's Achilles tear in practice Wednesday, opportunities will be there for Garoppolo to change a career-shadowing narrative and show he can strike deep.

2. STOP 'THAT DUDE'

Linebacker Fred Warner said Wednesday he's got a funny story about Colts running back Jonathan Taylor. You see, when Warner was coming out in the 2018 draft, teams would ask him who was the best running back he faced in his time at BYU, and his answer always was about a Wisconsin freshman he encountered. It was Jonathan Taylor, who ran for 128 yards.

"I said, 'Man, that dude is a beast,' " Warner recalled. "… For some reason he always stuck in my mind. I've got a lot of respect for Jon, Jonathan. He's got the breakaway speed, it looks deceptive on tape. He runs the ball hard. He's a really good back and we'll have to bring all 11."

Taylor, as a 2020 second-round draft pick, ran for 1,169 yards and 11 touchdowns last season, and this year he's off to a similar showing (472 yards, four touchdowns).

"If you're not where you need to be, in the right fit, this guy can take it to the house in a heartbeat," defensive coordinator DeMeco Ryans said. "Everybody has to be disciplined in proper gap and swarm and tackle. He's tough to get down."

Making the 49ers' job tougher could be the return of All-Pro guard Quenton Nelson. Even tougher: the 49ers won't have starting defensive tackle Javon Kinlaw (knee) nor Maurice Hurst (calf).

3. RESPECTING WENTZ

Before Carson Wentz ceded his starting job to a hot-shot rookie (Jalen Hurts) last year in Philadelphia – think: Garoppolo/Trey Lance balance, 2021 edition — Wentz rallied to win at Levi's Stadium in Week 4.

The 49ers need no reminder he can be just as dangerous as the recent quarterbacks who've beaten them (Aaron Rodgers, Russell Wilson and Kyler Murray).

"We never underestimate anyone and definitely not Carson," Ryans said. "He's a big-time play maker, can make all the throws and he's very elusive in pocket. He has an uncanny ability to keep plays alive and fire down field."

Wentz fired a 42-yard touchdown pass with 5:50 remaining to put the Eagles ahead of the 49ers in last year's meeting. This season, Wentz has overcome foot and ankle injuries, and he's thrown nine touchdown passes and just one interception. He's also been sacked at least twice each game with the Colts.

4. GET TO THE EDGE

With defensive tackle DeForest Buckner and linebacker Darius Leonard lurking up the spine of the field, the 49ers simply should run for the edge to recharge their offense. Right?

"That'd be awesome," offensive coordinator Mike McDaniel answered. "That would be a tough game plan to kind of produce, because they have different calls and they align differently, but also they're in the middle of the defense."

You see, Buckner and Leonard have a nose for the ball, so they'll be in hot pursuit wherever it goes.

"We'll do our best to make sure they're blocked," McDaniel added, "but when they aren't blocked make sure you protect the ball and do your best to strain because they are the real deal."

That memo goes out to starting running back Elijah Mitchell, who could be spelled by JaMycal Hasty's return from an ankle injury or else fellow rookie Trey Sermon. Backfield tosses to Deebo Samuel and Brandon Aiyuk also could spring the 49ers around the gate.

One issue: left tackle Trent Williams' sprained ankle. Even if he plays Sunday, how mobile will he be? If he's limited, perhaps the 49ers are best served not making him pull to the right side, and instead send right tackle Mike McGlinchey to the left.

5. BALL SECURITY

Rain will make the football slip from players' grasps. Odds are against the 49ers, if that's the case.

Last game, Leonard punched out his 11th career forced fumble, and no linebacker since 1999 has forced more after 48 career games, the Colts claimed.

Overall, the Colts have seven fumble recoveries and five interceptions, and that combines for the NFL's fourth-most takeaways. How surehanded are Mitchell, Sermon and Hasty carrying the ball? That is an element that must go in the 49ers' favor.

Defensively, the 49ers have only two takeaways (Dre Greenlaw's Week 1 pick-six, Dontae Johnson's Week 6 forced fumble).

Wentz has lost two fumbles. Same with Garoppolo.

"If it takes rain for us to get the ball, I'll be fired up," Ryans said. "Of course the ball becomes more of an issue in the rain when it comes to handling it. Rain or no rain, we've got to get it out."