Cryptogenic stroke constitutes over 30% of ischemic strokes, with patent foramen ovale (PFO) being identified as a significant etiological factor in nearly half of these cases. Consequently, accurate PFO diagnosis is clinically crucial. Established ultrasonic diagnostic techniques include transesophageal echocardiography (TEE), contrast-enhanced transthoracic echocardiography (c-TTE), and contrast-enhanced transcranial Doppler (c-TCD). Although TEE is the current reference standard, it is semi-invasive and often limited by inadequate Valsalva maneuver performance. Recently, the growing use of non-invasive coronary CT angiography (CCTA) has highlighted its potential for PFO diagnosis. In particular, the multimodal imaging that combines these diagnostic techniques holds promise for improving the accuracy of PFO detection, yet this approach has not received adequate attention in clinical practice. This article reviews pertinent research progress to enhance clinicians' understanding and application of innovative PFO diagnostic methods and multimodal imaging.