Bill Wippert/Associated Press

Rex Ryan and the Buffalo Bills, in what amounts to a must-win game, travel to Tennessee on Sunday for a matchup with Marcus Mariota and the Titans. The game, which starts at 1 p.m. ET and is televised on CBS, figures to be a defensive battle, as two young quarterbacks duke it out against two of the league’s most talented defenses.

For what feels like the umpteenth time already this season, Buffalo will be shorthanded. Star running back LeSean McCoy and upstart rookie back Karlos Williams were held out of practice on Friday, per Chris Brown of the team’s official website, and both are officially inactive for Sunday’s date with Tennessee.

McCoy, according to ESPN.com’s Mike Rodak, has a Grade 2 hamstring injury, which usually involves three to four weeks of recovery; Sunday’s game will be his second consecutive absence, and McCoy could feasibly be sidelined for quite a bit longer:

Watkins, however, participated in full drills on Friday, and his status is questionable for Sunday. Obviously, the Bills should do whatever is best for Watkins’ personal health and the future of his career. But the team’s playoff window is growing rapidly smaller, and it needs all the help it can get. Watkins would be a big boost in the absence of McCoy and Williams.

With that in mind, let’s take a look at the keys to a Buffalo victory on Sunday.

Buffalo’s Offensive Game Plan

There are two particular points to highlight here.

First, Tennessee cornerback Jason McCourty is set to make his season debut on Sunday. McCourty, whose twin brother Devin plays for the New England Patriots, is perhaps Tennessee’s most talented secondary defender, and his return bodes poorly for the Bills.

McCourty’s presence would make things tougher for Buffalo even if the Bills were at full strength. But he makes things especially complicated this week. Buffalo can’t expect to rely on its running game; without Williams and McCoy, no Buffalo wideout, with the possible exception of Percy Harvin, can simply outrun or overpower McCourty.

Plus, Buffalo quarterback Tyrod Taylor—despite his entirely solid start to the year—remains inexperienced and has been far more successful when limited to shorter, less risky throws. McCourty’s presence would normally make it even more important for Taylor to avoid downfield gambles. And Tennessee currently has the league’s best pass defense.

On the other hand, Buffalo leads the league with 22 plays of 20 yards or more, and without its usual running back corps, the Bills are obligated to rely on Taylor’s arm more than they might prefer. And Tennessee’s defense has a habit of surrendering big plays, as we saw in the Titans' matchups with the Cleveland Browns and Indianapolis Colts.

Which brings me to the second key point: Harvin and Buffalo tight end Charles Clay.

Clay has been superb in recent weeks. He had his best performance of the year in Week 3 against the Miami Dolphins, finishing with 82 yards and a touchdown on five receptions. Then, in last week’s loss to the New York Giants, Clay was even better, hauling in nine catches for 111 yards as the team’s lone offensive bright spot.

Harvin, meanwhile, has been by far Buffalo’s most consistent threat at the wide receiver position. He has yet to score since a 51-yard touchdown in Week 1 but has at least 11 more targets (26) than any other receiver on the team.

Together, Clay and Harvin represent nearly half (47 percent) of Taylor’s targets this year. That trio—Taylor, Clay and Harvin—will almost certainly be the team’s offensive focal point on Sunday. Taylor needs Clay to be his safety valve, someone who rescues broken plays by coming back to his quarterback and someone who plants himself firmly in the Titans’ defensive gaps.

What the Bills particularly need is for Harvin to stretch Tennessee’s secondary. His speed is undeniable, but Harvin’s offensive presence has been muted since at least Week 2, and his scoring absence can’t go on forever. Buffalo’s undermanned running game will benefit if Clay and Harvin are targeted early and often.

Defensive Game Plan

First, I’m obligated to mention penalties yet again. ESPN’s Rodak reported on Friday that star defensive end Jerry Hughes was fined over $23,000 by the NFL for his actions last week, when he was called for unsportsmanlike conduct after cursing out a referee.

Frankly, it’s remarkable that no other Bills player has been fined, as the team has racked up some 47 penalties (at a cost of 428 yards and numerous scoring opportunities) in just four games this year.

In fairness, the penalty problem has not come solely on the defensive side of the ball—several offensive violations have nullified Buffalo points and first downs—but it will be especially crucial on Sunday for the defensive unit to play within the rules. Tennessee star Mariota is talented and poised, but he’s young and not as unflappable as he may appear. The Bills need to rattle him early, not give him free yards.

Second, Buffalo’s secondary has two fairly simple tasks this week: Stop Delanie Walker, and stop Kendall Wright. That pair accounts for a third of Mariota’s targets, 38 percent of his yards and three of his eight touchdowns. And Tennessee’s running game has been entirely disappointing, as touted running back Bishop Sankey has failed to live up to preseason hype.

It’s worth noting that rookie wideout Dorial Green-Beckham, an absurdly imposing physical presence (he’s 6’5” and weighs 237 pounds), has just three catches on five targets—but two of those catches went for touchdowns. His athletic abilities make him an ideal red-zone target, and Buffalo should be wary of his presence in goal-to-go situations. The Titans rank second in the NFL in terms of touchdowns scored per red-zone possession, at 76.9 percent on the year, per Chris Brown of the team's official website.

However, despite his scores, Green-Beckham has seen extremely limited playing time, and Walker and Wright remain the most consistently dangerous weapons available to Mariota. Luckily for Buffalo, its secondary has not been the team’s problem this year, and Wright will likely see a lot of Defensive Rookie of the Month Ronald Darby.

Darby leads the league in passes defended, and his hot start has thoroughly impressed both fans and his coaching staff. His total lack of preseason consistency has been replaced by physical, aggressive, energetic play, and Darby has emerged as an unlikely cornerstone for a Buffalo secondary wracked (like the rest of the team) by injuries.

Summarily, Buffalo’s defensive game plan should focus on Walker and Wright. The defense should be careful to avoid red-zone situations where Green-Beckham is matched up with an undersized cornerback. And, as if it weren’t obvious, it should make an extra-concerted effort to avoid penalties.

X-Factor: Boobie Dixon

Penalties, Taylor, Darby, Clay—all are critical to Buffalo’s success, this week and throughout the year. But on Sunday, the real key will be Boobie Dixon.

Buffalo made a big offseason splash when they signed McCoy. And Karlos Williams has been an absolute revelation through Week 4, scoring touchdowns in each appearance and routinely jetting past defensive linemen. But as of yet, McCoy has never looked healthy, and Williams has benefited from his relative anonymity.

Which leads us to Dixon, who scored a one-yard touchdown in Week 1 but has compiled zero cumulative rushing yards and just eight carries in 2015. At 6’1” and 233 pounds, Dixon is a bullish, vertical ball-carrier with the strength to take contact and the speed to reach outside blocks. (Incidentally, his path to the NFL is also an incredible story).

What the Bills need is balance. Either Taylor needs to find Clay and Harvin early and often, opening things up for the depleted running game. Or Dixon needs to make an early splash and take the pressure off Taylor.

One way or the other, Buffalo needs to win this game, and that will require someone stepping up. The Bills can win without a top-notch performance from Dixon, or from Clay, or from Harvin. But they either need consistent output from that trio or a standout game from one of the three.

Prediction: Bills 24, Titans 21