The rivals will take part in a town hall event jointly hosted by CNN and TV One at Ohio State University and face questions from Buckeye State voters as they vie for the support of blue collar and minority voters who underpin the Democratic coalition.
The encounter, in which Clinton and Sanders will appear one after the other with CNN's Jake Tapper and TV One's Roland Martin starting at 8 p.m. ET, takes place in the wake of Sanders' surprise victory in the Michigan primary last week, which raised his hopes of competing with Clinton across Midwestern Rust Belt states.
But Clinton, who has so far built a more diverse constituency resting especially on African-American voters and Hispanics, appears to have the edge going into Tuesday's primaries in Ohio, Florida, Illinois, Missouri and North Carolina.
Still, Sanders has high hopes of good results in the Midwest in particular and has been driving his message that the economy is stacked against working Americans and underpinned by a corrupt political system.
The town hall meeting will also give both candidates a chance to renew their condemnation of the violence taking place at Donald Trump's rallies as they make the wider argument that the Republican front-runner is unfit for the presidency.
Sanders has been accused by Trump of orchestrating protests at the latter's rallies that have degenerated into clashes with the billionaire businessman's supporters.
The Vermont senator is also stepping up attacks on Clinton over free trade deals, emerging as a dominant issue of the election amid a belief in industrial states that they are to blame for the flight of blue collar jobs abroad and lingering economic blight.
On Saturday, Sanders rebuked Clinton over her role in conceiving of the Trans-Pacific Partnership, a vast trade deal linking Asia and the Western Hemisphere. It is a lynchpin of President Barack Obama's pivot-to-Asia strategy that she helped implement as secretary of state.
"I hear Secretary Clinton is in Ohio tonight talking about how concerned she is about the auto industry -- an industry decimated by the North American Free Trade Agreement and normalized trade with China. She supported those bad deals. I opposed them," Sanders said.
"Now she says she wants to make it tougher for automobiles to be imported to this country under the disastrous Trans-Pacific Partnership. That's the deal she called the 'gold standard' when she was secretary of state," he continued.
Sanders has called for the pact to be scrapped while Clinton has called for it to be improved, and the Vermont senator is trying to take advantage of the difference in their approaches.
"I have a message for Secretary Clinton: We shouldn't re-negotiate the Pacific trade proposal," he said. "We should kill this unfettered free trade agreement which would cost us nearly half a million jobs."
Clinton, meanwhile, chose to go after Sanders over his attacks that she is not sufficiently progressive, questioning his role when she was fighting for expanding health care as first lady.
"We are going to pull together and stay together and stand up against those powerful forces. And I always get a little chuckle when I hear my opponent talking about doing it," Clinton said on Saturday. "Well, I don't know where he was when I was trying to get health care in '93 and '94, standing up (against) the insurance companies, standing up against the drug companies."
The Sanders camp hit back quickly, tweeting a photo of Sanders standing behind Clinton at an event at Dartmouth College on December 7, 1993.
"I am grateful that Congressman Sanders could join us today from Vermont," Clinton said at that event.
Tuesday's primaries are hugely significant because they make up the third-highest allocation of delegates available on a single day in the Democratic presidential race.
A new poll by The Wall Street Journal and NBC published on Sunday shows Clinton leading Sanders for the three biggest prizes available on Tuesday. She is up 61% to 34% on Sanders in Florida, leads him by 58% to 38% in Ohio and by six points in Illinois.
Still, Sanders will be hoping that the last Tuesday's events are an omen for this week after he went into the Michigan primary trailing badly in polls but still managed to best Clinton.
The former secretary of state, however, is looking to further bolster her lead in delegates over Sanders on Tuesday.
According to CNN estimates, Clinton has 1,244 delegates (including 772 pledged delegates and 472 superdelegates). Sanders has 574 delegates (including 551 pledged delegates and 472 superdelegates). Superdelegates are party officials and lawmakers who can vote at the convention and have already made their intentions clear.