Today, coronary artery disease (CAD) continues to be a prominent cause of death worldwide. A reliable assessment of coronary stenosis represents a prerequisite for the appropriate management of CAD. Nevertheless, there are still major challenges pertaining to some limitations of current imaging and functional diagnostic modalities. The present review summarizes the current data on invasive functional and intracoronary imaging assessment using optical coherence tomography (OCT), and intravascular ultrasound (IVUS). Amongst the functional parameters—on top of fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR)—we point to novel angiography-based measures such as quantitative flow ratio (QFR), vessel fractional flow reserve (vFFR), angiography-derived fractional flow reserve (FFRangio), and computed tomography-derived flow fractional reserve (FFR-CT), as well as hybrid approaches focusing on optical flow ratio (OFR), computational fluid dynamics and attempts to quantify the forces exaggerated by blood on the coronary plaque and vessel wall.