Was it the decline in fur value? The modern world encroaching? What year might you have found the last true mountain men? 1880 or so?
With the over-hunting of beaver in Europe, there was an incredibly high value placed on beaver pelts for making hats in the 17th c., and the beaver trade became immensely disruptive to the balances of powers and trade between Native Nations almost from the outset of European contact in North America. As traders and trading networks were established, by the early 1800's western Native bands and the Mountain Men could sell their furs to nearby posts of merchants like the Hudson's Bay Company, or John Jacob Astor's The American Fur Company, which meant they could stay in the field trapping. However, that seems to have created an oversupply in pelts and a price drop by the late 1700's. The value of beaver pelts dropped further when hatters started making hats with silk instead of fur felt circa 1830. Beaver also became harder to find, from habitat loss in the Midwest US (where forest became cropland) and over-trapping in the West and Rockies. Astor's American Fur Company went bankrupt in 1842, stopped trading in 1847. In the 1840's sensible trappers like Jim Bridger found it paid better to be a guide to military expeditions and wagon trains of settlers heading west.
I am not sure if anyone has identified a "last" Mountain Man, but the place of the Mountain Man ( White, male, alone, heroic) in the fur trade has perhaps gotten too much attention. It was far bigger than them. There had been plenty of Native trappers before characters like Hugh Glass arrived, and in western Canada in the early 1800's whole Méti communities were dependent on commercial beaver trapping and also on commercial buffalo hunting to provision trappers and traders ( a situation that led to the Pemmican Wars). It was also far bigger than the Rockies- fur trapping would continue to be a source of income in wild places like Labrador for quite a long time after 1850, even if it was not always in beaver, and included muskrat and mink.
Ronda, J. P. (1993). The Fur Trade Issue. Montana: The Magazine of Western History, 43(1)