There were a sufficient number of outsize and heavy payloads that no other airlifter could carry to make operating the An-225 profitable, but I assume that’s after writing off the R&D and manufacturing cost which were funded by the Energia/Buran program. There are cargoes which would have had to have been shipped in pieces and assembled at the destination or shipped via sea (where possible) had the plane not been available.
Outsize air cargo is a well established sector, dating back to the Pregnant Guppy, discussed here on 2022-04-11. A total of 4 Boeing Dreamlifter, 5 Airbus Beluga, and 6 Beluga XL planes have been built.