Argentine superstar Messi scored once and provided the assists for all Inter's other goals, with Tadeo Allende scoring twice and Mateo Silvetti adding the other to send Miami into next Saturday's Eastern Conference championship.
Inter Miami will play host to New York City FC to decide a berth in the MLS Cup final after visiting City upset top seed Philadelphia 1-0 in the night's other match.
On Sunday's evidence, third-seeded Miami will head into next weekend's fixture brimming with confidence after laying on a performance of pace and precision to dispatch second seeds Cincinnati.
Miami coach Javier Mascherano lavished praise on Messi and his team-mates after a performance he described as near-perfection.
"I'm proud of how the team played on a very difficult pitch against a very difficult opponent," Mascherano said.
"The players showed incredible character and played a practically perfect match.
"It's an honor and a privilege not only to manage Leo but this group of players. We know what Leo is capable of; he proves it every weekend. Today, he did another incredible job off the ball, because we already know what he's capable of with it."
A sold out crowd of just over 26,000 had packed Cincinnati's TQL Stadium hoping to see the home side score an upset over Javier Mascherano's star-studded Inter team.
But the home side were made to pay for failing to take their chances in a bright opening, with striker Kevin Denkey forcing a good save from Miami goalkeeper Rocco Rios Novo after 15 minutes.
Miami took the lead moments later, when Messi picked out Argentine teenager Silvetti - who had started instead of veteran Luis Suarez - with an incisive path down the left flank.
Silvetti duly returned the favour with a pinpoint cross into the area that Messi coolly nodded home to make it 1-0.
Cincinnati squandered a chance to draw level in the 22nd minute when Venezuelan forward Ender Echenique burst into space but dragged his shot wide.
Thereafter it was all Miami, and Messi might have made it 2-0 on 27 minutes, advancing into space but hooking his shot wide of the post.
Inter's more incisive attacking play got its reward, though, on 57 minutes, when Messi found Silvetti on the edge of the area, where the Argentina under-20 international curled home to make it 2-0.
As an increasingly desperate Cincinnati chased the game, more space opened up, and with Messi pulling the strings it was only a matter of time before Miami increased their lead.
Messi threaded a pass to Allende to make it 3-0 on 62 minutes, and then sprang the offside trap once more on 74 minutes to set up Allende for the fourth.
The winners of next weekend's Eastern and Western Conference finals meet in the MLS Cup championship game on December 6.
Vancouver will play in the West final against the winner of Monday's matchup between top-seed San Diego and Minnesota United.