Matchups to target is one of the most important factors to consider when crafting your fantasy lineup each week. In MLS, where home field provides a greater advantage than most leagues, players frequently deal with cross-country travel and multiple competitions, which can impact performance. It’s important to consider these factors, as well as performance metrics such as home/away form and player injuries to pinpoint favorable matchups. Each week I’ll focus on a few matchups you should target to help your team collect those precious fantasy points. Here are some to keep an eye on in round six:

Inter Miami vs Philadelphia Union (Sat, 7:30pm ET)

This is a big early-season matchup between two of the Eastern Conference’s top teams, both ranking in the top-10 of the league in npxG/90 and top-5 in G/90. Both have also had a couple matches where their defenses looked less than airtight, and I expect both attacks to come out flying. Aside from the possible absence of Lionel Messi, who also missed the international window due to injury, both sides should have their stars available for Saturday’s showdown in Miami. As with most Miami games, this one has the potential to be a shootout—hopefully delivering big fantasy returns. 

PLAYER TARGETS:

• Lionel Messi (FWD, MIA) If available
• Luis Suarez (FWD, MIA)
• Telasco Segovia (MID, MIA)
• Daniel Gazdag (MID, PHI)
• Tai Baribo (FWD, PHI)
• Kai Wagner (DEF, PHI)

Minnesota United vs Real Salt Lake (Sat, 7:30pm CT)

Minnesota enter this matchup on a four-game unbeaten streak, and although their last two results were draws they still scored 5 goals in those two matches. They’ll be eager to get back in the win column against an inconsistent Real Salt Lake side. Forward Kelvin Yeboah is a certified stud who leads the league in shots/90. Minnesota rank in the top three in npxG, which isn’t too surprising given all their firepower, while RSL sit near the bottom for npxG conceded. Given those statistics, I expect Minnesota to dominate at home, secure three points, and hopefully produce solid fantasy returns in the process. 

PLAYER TARGETS:

• Kelvin Yeboah (FWD, MIN)
• Bongi Hlongwane (DEF, MIN)
• Tani Oluwaseyi (FWD, MIN)
• Diego Luna (MID, RSL)

Nashville SC vs FC Cincinnati (Sat, 8:30pm ET)

Nashville are off to their best-ever start in MLS, picking up ten points through five weeks—good for joint-second place in the Eastern Conference. Meanwhile, Cincinnati haven’t quite hit their stride in 2025, sitting 10th in the East with just one win in their last seven matches. With Nashville’s attack starting to click (8 goals last 3 matches) and Cincy’s defensive struggles so far away from home (4 GA in 2 matches), don’t be surprised if Roman Celentano is picking the ball out of his net a few times. And Nashville’s defense has been even better, not allowing more than 0.5 xG in any home match. Unless Evander is able to conjure up more magic this week, it could be a long day at GEODIS Park. 

PLAYER TARGETS:

• Hany Mukhtar (MID, NSH)
• Sam Surridge (FWD, NSH)
• Evander (MID, CIN)
• Luca Orellano (DEF, CIN)

LA Galaxy vs Orlando City (Sat, 10:30pm ET)

This matchup to target has all the ingredients needed for a goal-fest, and it should have fantasy managers licking their chops. LA Galaxy and Orlando have both been leaky at the back this year, with the Galaxy conceding 10 goals and Orlando conceding 11 goals. While Orlando have struggled defensively, they lead the league in goals scored (12) and are averaging an impressive 2.0 npxG/90. Even with the Galaxy’s early-season struggles, they should be able to capitalize on Orlando’s defense that has allowed 2.6 goals/90–worst in MLS. Being at home will give the Galaxy’s attack an extra boost, and with both defenses struggling, there should be goals on both sides—likely resulting in big fantasy performances.

PLAYER TARGETS:

• Gabriel Pec (FWD, LAG)
• Christian Ramirez (FWD, LAG)
• Martin Ojeda (MID, ORL)
• Luis Muriel (FWD, ORL)

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Contributor: Eli Redpath, @vurkes on Discord