For Ducati, the V4 layout at 90° is the utmost expression of sportiness for a motorcycle engine. It is no coincidence that it is the same solution used in the MotoGP Desmosedici engines. The 90° V layout of the cylinders creates a natural balancing of first-order forces without the need to resort to a balance shaft to eliminate the vibrations that notoriously entail increases in weight and power absorption. In addition to this primary benefit, which is extremely important for the reliability and mechanical efficiency of an engine that reaches rotation speeds greater than 14,000 rpm, there are others that make the configuration chosen by Ducati the most technically refined.

Compared to a classic in-line four-cylinder, the lateral compactness of the V-engine allows greater centralisation of the masses and makes it possible to limit the weight on the front end of the bike. Furthermore, the shorter crankshaft generates a smaller gyroscopic effect. All these aspects have a positive impact on the bike's dynamics, helping to make it light and fast when changing directions. The large space available between the V of the cylinders made it possible to position the water pump and have a large volume airbox (12.8 litres) to allow the Desmosedici Stradale to breathe better.

The optimal integration of engine and chassis is a fundamental concept behind every Ducati project. That is why the Desmosedici Stradale was developed to be mounted rotated backwards by 42°, like the Ducati MotoGP engines, to optimise weight distribution, use more extensive radiators and to shift the swinging arm pivot forwards as much as possible. The Desmosedici Stradale was also designed to be a structural element of the frame. Connections to the main frame were added to the front of the upper casing and in the head of the rear bank. The engine block also acts as a connection for the rear suspension and swinging arm.

On normal motorcycles the crankshaft rotates in the same direction as the wheels. In contrast, in MotoGP the counter-rotating crankshaft rotates in the opposite direction. The Ducati engine specialists have borrowed this technical solution from the racing models for the same reasons it was applied in the competitive world. In fact, this solution has advantages related to two aspects of physics: the gyroscopic effect and inertia. The counter-rotating crankshaft makes it possible to compensate part of the gyroscopic effect produced by the wheels while riding, and this results in improved handling and a motorcycle that is more agile when changing direction. The second advantage is related to inertia (that is, the tendency of an object to oppose a change in state) both of the vehicle and the rotating engine parts. During acceleration, the driving torque transmitted to the ground pushes the vehicle, which reacts by generating a tendency to do a wheelie. Due to inertia, the counter-rotating crankshaft generates a torque in the opposite direction, which thus tends to lower the front end thereby reducing the wheelie phenomenon, with also benefits acceleration. Likewise, during braking or fast decelerations, the motorcycle experiences a reaction that tends towards rear lift-up, but the crankshaft also undergoes a deceleration (reduced rpms) and this results in an inertial torque in the opposite direction that counters the force seeking to lift the rear end. Consequently, both in acceleration and braking, the adoption of the counter-rotating shaft provides positive effects. Clearly, this layout requires an additional toothed wheel, the so-called idle wheel, which is necessary to transfer the crankshaft motion to the gearbox and then to the wheels so as to provide the correct rotation for the direction of travel.

The 70° offset of the crank pins combined with the 90° V-engine layout generates a firing order that Ducati has called "Twin Pulse" because it is as if the engine were reproducing the firing sequence of a twin cylinder. The peculiarity lies in the rapid firing of the two cylinders on the left side and then on the right side of the motorcycle. In the timing diagram, the firings are situated at 0°, 90°, 290° and 380°. This particular firing order gives the V4 a sound that is quite similar to that of the Desmosedici MotoGP. In practice, imagining a cycle that starts with 0°, the first cylinder of the front bank "fires", generator side, followed, after only 90° of rotation, by the rear bank cylinder on the same side. Then there is an interval during which the engine does not generate drive torque until the firings 90° from each other in the two cylinders on the clutch side. The "Twin Pulse" firing order, besides producing a unique exhaust sound unlike any other motorcycle, music to the ears of a true enthusiast, generates a type of power that was judged to be the best by the Ducati MotoGP riders as it generates important advantages at the power level and therefore the rideability of the motorcycle, especially when cornering and coming out of curves.

Like the MotoGP engines, the Desmosedici Stradale uses a semi-dry casing lubrication with delivery and recovery stages to ensure proper lubrication of all moving parts at all times. The oil pump, driven by a chain, consists of four stages, one for lobe delivery and three for recovery, one with gears to draw oil from the heads through two ducts, while the other two pumps have lobes and ensure effective recovery of lubricating oil in any condition of engine use, while maintaining the engine crankcase underneath the pistons under controlled constant vacuum conditions, reducing losses due to ventilation, that is, the power absorption caused by the aerodynamic resistance offered by the air and the beating of the oil present in the connecting rod compartment. The oil tank, which also serves as a filter housing, is situated in a magnesium oil sump mounted under the crankcase and connected to the gearbox compartment, but separate from the crankcase. For cooling the oil a dedicated radiator is used, secured below the water cooler.