MLB commissioner Rob Manfred seems to be open to changing just about anything about baseball. The latest topic to come up is the idea of shortening the regular season. Manfred says "I don't think it would be impossible to go back to 154 (games)."
Manfred goes on to say shortening it to something like 110 games would be problematic, because "that will throw all our numbers out of whack." The point he was making was the MLB already had a 154-game for many years (the AL switched to 162 games in 1961, the National League made the change in 1962... it seems sort of strange that the two leagues played a different number of games for one season, but the two leagues were not nearly as tightly entwined then as they are today), and so such a change would be a return to something, not a switch to something entirely new.
The other numbers Manfred could have been referring to (when he talks about things getting out of whack), because they're the ones owners are unlikely to accept such a drastic change to, are the revenue streams that would be impacted. Eight fewer games in the season means 8 fewer games in the TV and radio contracts, it means 4 fewer home games for ticket, parking, concession, and souvenir sales.
Millions of dollars in revenues would disappear, making this a non-starter for most owners. In theory the players would be for it, because it would mean either their offseason would get a bit longer or (and I imagine most of them would prefer this) more days off during the season. On the other hand, lower revenues are going to impact them too, because their salaries come from those revenues. Most people would like more time off from their job, but not everyone is willing to give up salary to gain that time off.
My preference would be give players a few extra days by having each team host two or three scheduled doubleheaders a season, though I'm not sure a majority of players would actually prefer that, and I'm sure most owners wouldn't, because that changes hurts their revenue streams too (though not nearly as much).
Even if money weren't an issue, I wouldn't want only 154 games. It's not that I think 162 is precisely the right number; I'm used to 162 though, and while I get that records from different eras are already skewed by the prior lengthening of the schedule (among many other factors that make comparing 1945 and 2015 tricky), I wasn't around for the 154-game years. In my lifetime, baseball has always been 162 games, and that's where I want to keep it.
Fortunately for me, millions and millions of dollars are on my side.