The Union played out a stalemate with reigning MLS Cup holders Columbus Crew in their opening match, while Inter were beaten 3-2 by Los Angeles Galaxy.
Last weekend's clash between the Union and Columbus was supposed to be the pick of the gameweek one action, but neither side could find a breakthrough in the stalemate.
Both sides hit the post, while the Crews had a penalty awarded and then ruled out, in what was a largely disappointing contest for the neutral.
Still, a point against the MLS Cup holders is not the worst result for Philadelphia, who themselves enjoyed an impressive 2020 by winning the Supporters' Shield.
Jim Curtin's side have now played three times this term, having also defeated Costa Rican outfit Deportivo Saprissa 5-0 on aggregate in the CONCACAF Champions League last 16.
Getting three points on the board against Inter Miami is the next target, but the visitors will themselves be eager to get off the mark after their slender loss to the Galaxy.
The game looked set to finish all square at that point, but Sacha Kljestan found a winner with nine minutes remaining to deny Neville a maiden MLS victory.
Inter endured a disrupted pre-season, largely owing to coronavirus restrictions, and now face a difficult contest at Subaru Park.
The Union have won nine of their last 10 home league matches, albeit the exception being their most recent such game there, while Inter have lost four in a row on their travels.
Ryan Shawcross was an unused substitute against the Galaxy, with Neville opting to go with a tried-and-trusted setup.
Kacper Przybylko scored in both legs of Philadelphia's win over Saprissa, but he fired a blank in the stalemate with Columbus.
Philadelphia Union possible starting lineup:
Blake; Mbaizo, Glesnes, Elliott, Wagner; Bedoya, Martinez, Flach; Monteiro; Santos, Przybylko
Inter Miami possible starting lineup:
McCarthy; Leerdam, Figal, Pirez, Jones; Matuidi, Gregore; Morgan, Pizarro, Pellegrini; Higuain
We say: Philadelphia Union 1-0 Inter Miami
The home side will be looking to build on what can be considered a positive point against the Crew in their opening match when Inter visit Subaru Park this weekend.
Neville's men were a little unfortunate to lose against the Galaxy, having twice led in that one, but we can see them losing again here.