The Enzo benefited from an entirely new engine design which carried the project name F140. Design features included a 65° V, a displacement of 5998 cc. (365.87 cu in) and an 11.2:1 compression ratio. There are four valves per cylinder, a departure from some current road cars which can boast about their five valves per cylinder. The block and heads are cast aluminum with press fit Nikasil sleeves in the cylinders. Timing is supplied by four overhead camshafts which feature variable timing. Also accomodating changeable demands on the engine are variable length telescope-cone type intake runners. The pistons are coupled to a lightweight seven main bearing crankshaft by titanium connecting rods. The weight of the F140 engine is 225 kg (496 lb). Redline is 8000 RPM.

Engine control is via a Bosch Motronic ME7, which commands the multiple port fuel injection, the spark plugs and the drive-by-wire fuel system. In appreciation of the massive cornering power the Enzo is capable of, a Formula One wraparound dry sump lubricating system is employed.

Output is rated at 485 kW (660 bhp) at 7800 rpm. This works out to 110 bhp per liter of engine or 1.8 bhp per cubic inch of displacement, an amazing number for a street engine without boost assist. Further evidence of advanced engineering can be found in the fact that this phenomenal engine meets world wide emissions and noise standards.