One embodiment provides a system for cardiac stimulation optimization utilizing cardiac asynchrony and pulse pressure data. The system includes: an analysis circuitry to receive cardiac signals collected at two locations of a patient's heart during an application to the heart of stimulation in accordance with multiple (VV) delay intervals, calculate an asynchrony index for the VV delay intervals, and determine one of the VV intervals as optimal based on the asynchrony index for that VV interval; an implantable stimulation device to cycle through the VV intervals while applying the stimulation, and further configured to cycle through atrioventricular (AV) delay intervals while applying additional stimulation in accordance with the optimal VV delay interval; and an arterial pulse pressure sensor to measure arterial pulse pressure during the application of the additional stimulation, wherein the analysis circuitry determines one of the AV delay intervals as optimal based on the arterial pulse pressure measured.