The Cameroon striker opened the scoring in the 34th minute as the Swiss side took a shock lead, but their advantage only lasted 10 minutes before Borja Mayoral levelled the contest.
Riccardo Calafiori then netted for Roma just before the hour mark as they moved ahead of the visitors, before Edin Dzeko scored in the 81st minute to round off a victory for the home side.
Guinea’s Mohamed Ali Camara was dismissed a minute later as the contest went from bad to worse for the visiting Young Boys.
Despite their defeat, Gerardo Seoane’s side still remain in the hunt for qualification to the knockout stages, and will advance to the next round if they avoid defeat by CFR Cluj at home in matchday six.
Before Thursday’s defeat, Young Boys had gone three games without defeat in the Europa League, and while they were previously held by Cluj in Romania, they are favourites to advance to the next round alongside Roma.
Nsame, who was linked with a move to Tottenham Hotspur earlier in the year, has been in superb form so far this season.
His opener against Roma was his third in five Europa League group-stage appearances so far this term, having previously found the net against CSKA Sofia and against Roma in the first match between the pair.
Last season, he netted 32 goals in 32 top flight games to become the all-time top scorer in a single Swiss top flight season, surpassing the record previously held by Ivory Coast international Seydou Doumbia.
The Elephants international, who’s currently back in Switzerland with FC Sion, had scored 30 goals in 32 league outings for Young Boys during the 2009-10 campaign.