Ontario has never wanted to leave Canada. However, northern Ontario has wanted to split from southern Ontario and form its own province within Canada. Source: I was born and grew up in northwestern Ontario and there was a fair amount of dislike of southern Ontario, but also strong pro-Canadian sentiment. In summary:

Resource Revenue - Northern residents feel local profits from mining, forestry, and hydro generation are siphoned to Southern Ontario with insufficient local reinvestment.

Transportation & Services - Higher gas taxes, highway maintenance backlogs, winter road safety, and limited transit (e.g., the elimination of Trans-Canada Greyhound bus service. Many small towns on the Trans-Canada highway are now almost impossible to reach without a car, without spending a lot more time and money).

Policy Disconnect - One-size-fits-all regulations designed for urban Toronto often fit poorly in northern wilderness environments.

Political Power - Northern Ontario holds roughly 10–13 provincial seats out of 124, making it difficult for northern MPs or MPPs to influence policy regardless of who forms government.