Edin Dzeko, Henrikh Mkhitaryan and Cengiz Under lead the attack, as Roma need at least a point with Wolfsberg to reach the Europa League knockouts.
It kicks off at the Stadio Olimpico at 20.00 GMT.
The Giallorossi need only a point to secure their place in the Europa League knockouts and could also still win the group, as they go in on eight points alongside Borussia Monchengladbach.
Coach Paulo Fonseca can only rotate so much, as some decisions are forced upon him by injuries to Justin Kluivert, Chris Smalling, Davide Santon, Javier Pastore, Bryan Cristante, Davide Santon and Davide Zappacosta.
Alessandro Florenzi and Antonio Mirante get rare starts, while Federico Fazio returns from injury.
Austrian side Wolfsberg started this Europa League campaign with a shock 4-0 win away to Borussia Monchengladbach, but it has been all downhill from there.
Soldo, Baummgartner and Schmerbock are all out of action for the visitors,
Roma: Mirante; Florenzi, Mancini, Fazio, Spinazzola; Diawara, Veretout; Under, Mkhitaryan, Perotti; Dzeko
Roma bench: Pau Lopez, Juan Jesus, Pellegrini, Kolarov, Kalinic, Zaniolo, Antonucci
Wolfsberg: Kofler; Novak, Sollbauer, Rnic, Schmitz; Schmid, Sprangler, Wernitzing; Liendl; Weissman, Niangbo
Wolfsberg bench: Kuttin, Gollner, Peric, Steiger, Schofl, Hodzic, Golles.
Ref: Craig Pawson (ENG)
Watch Serie A live in the UK on Premier Sports for just £9.99 per month including live LaLiga, Eredivisie, Scottish Cup Football and more. Visit: https://subscribe.premiersports.tv/