The Wales Millennium Centre (WMC) has rejected calls to cancel its staging of the musical, Jerry Springer the Opera.
The opera features Jesus and God as guests on Springer's TV show
The award-winning musical, which features Jesus, Mary and God as characters, begins a six-day run at the WMC in Cardiff next week.
More than 100 church leaders have signed a letter calling for the cancellation of the show.
The WMC said art should both challenge and entertain, adding it had met church leaders to discuss the show.
Jerry Springer - The Opera, a parody of the US TV show, has won several awards, but some Christians have claimed the content is offensive.
The musical features Jesus, Mary and God as guests on Jerry Springer's TV talk show and up to 300 swear words.
The award-winning West End production was seen by 425,000 people and was watched by an audience of 2.4 million when it was broadcast on BBC Two in January 2005.
Its content led to the BBC receiving a record 63,000 complaints as well as many messages of support.
The Cardiff performances, between 12 June and 17 June, are part of the show's 21-venue tour of the UK.
The WMC has previously said that it would allow Christian literature to be distributed in the centre's foyer over the period the show is there.
But Monday's letter, signed by representatives of more than 100 churches in Cardiff and across south Wales, called on the venue to cancel the show.
Reverend Peter Naylor, of Llandaff Presbyterian Church (Reformed), in Cardiff, said: "Christians in Cardiff and south Wales are deeply offended that a national venue paid for by our tax money is being used to mock God and his son, Jesus Christ, in the most vulgar way.
"I cannot imagine the Millennium Centre staging a show which mocked any other religion in this way.
The show will run for six days at the Wales Millennium Centre in June
"The show is gratuitously offensive. Many people are unaware of the actual content of the production."
The letter follows criticism of the show from the Archbishop of Wales, Dr Barry Morgan, who last month said the show was "blasphemous and gratuitously offensive".
But in a statement, the WMC said it was committed to staging art that would "push the boundaries".
The statement read: "History is full of controversial pieces of art which today appear tame.
"Jerry Springer - The Opera may be thought provoking, but then again art should both challenge and entertain people.
"WMC respects the rights of people to express their views and we have dealt sensitively with all those who have written to us with their comments.
"We have also met with a number of church leaders, including the Rev Dr Peter Naylor, and listened to their concerns."
The WMC was supported by theatre director Michael Bogdanov who said: "If you give in to what is, in fact, a minority protest then you are on a slippery slope not just to censorship but to a kind of Stalinist regime where everything is repressed."