Mandel is a good candidate for Ohio, but I'm not sure Ohio is Republican enough to pull off a Republican gain in 2018. I'd expect it to swing towards him, though.
Hard to say when the next opportunity after 2018 will be, though. He does already have two statewide victories under his belt, but it would probably seem obsessive if he runs for this again in 2024 (on the other hand, John Neely Kennedy was elected to the Senate on his third attempt and second party; as was, amusingly enough, Bernie Sanders). I assume if he loses he'll run for a different statewide office in 2022.
Unless Democrats sweep the row offices, which they obviously won't, he's going to be in a tough fight to actually find something to get elected to in 2022. It's not like the current statewide Republicans like him.
This. He's out in 2018, and maybe has a shot in 2020 at remaining somewhat relevant depending on how gerrymandered the Congressional, State Senate, or State House seat his home in Beechwood falls into. He could probably garner enough local support to win there if it's a Republican seat. Otherwise he's waiting till 2022 to maybe try taking out any Democratic office-holders, though by then I suspect the statewide party will have had their fill of him, particularly compared to its ranks deep bench.
If he doesn't have a readily-winnable legislative seat to run for in 20, I wouldn't be surprised if he just cashed in and quit politics, or at least kept his powder dry until 22.
The only thing keeping me from not saying never is Mike DeWine.