Messi's red-hot season was rocked on Wednesday as Miami stumbled to a 3-0 defeat against FC Cincinnati.
But the Argentinian superstar was back to his inspired best as Miami turned on the style at the Sports Illustrated Stadium in Harrison, New Jersey to record an emphatic victory.
The Red Bulls had threatened to deliver another upset after Alexander Hack bundled home a 14th-minute opener to fire the hosts into an early lead.
But Messi swiftly orchestrated Inter Miami's recovery from that setback, providing a sublime pass to set up former Barcelona team-mate Jordi Alba's equaliser in the 24th minute.
Messi then combined with Alba for Miami's second goal, producing another brilliant pass to pick out the Spaniard, who crossed for Telasco Segovia to prod home on 27 minutes.
Segovia then swept in his second of the night deep into first-half stoppage time to leave Miami firmly in control.
Messi then took over in the second half as Miami cut loose.
A majestic through ball by another former Barcelona teammate, Sergio Busquets, sent the Argentine World Cup-winner racing through on goal in the 60th minute.
Messi took his time and coolly feinted to wrongfoot Red Bulls goalkeeper Carlos Coronel before tucking away the finish for 4-1.
Another Barcelona old boys combination delivered Messi's second. Luis Suarez crossed from the left and Messi controlled on the edge of the six-yard box to send a thumping finish past Coronel.