With the advent of endovascular therapy, conventional angiography has replaced histology as a diagnostic gold standard for fibromuscular dysplasia (FMD). However, angiographic findings are not precisely diagnostic in isolated focal renal artery stenosis (RAS) in FMD. Optical coherence tomography (OCT) imaging by reflecting in vivo histology may improve the diagnostic accuracy in such cases. Restenosis following balloon angioplasty of RAS in FMD occurs frequently and often requires optimized reintervention. However, the role of OCT in the diagnostic evaluation of focal RAS in FMD and in optimizing the intervention is not well studied. We present a young female with resistant secondary hypertension due to bilateral focal RAS on angiography. In the absence of an angiographic string of beads appearance, the diagnoses remained uncertain. However, OCT imaging diagnosed a multifocal disease with characteristic changes of fibro-medial dysplasia, akin to its histological description in the literature. The patient underwent bilateral balloon angioplasty with good angiographic results. After one year on follow-up, relapse of uncontrolled systemic hypertension occurred due to bilateral restenosis. Despite a satisfactory repeat balloon angioplasty of the left-sided re-stenotic lesion, a significant residual pressure gradient persisted. Usage of OCT guided oversized balloon and stent safely achieved good results with complete resolution of the pressure gradient. Right renal artery stenosis required balloon angioplasty alone. She had complete resolution of hypertension without any medications at six months of follow-up. In conclusion, OCT can supplement other diagnostic modalities in providing a proper diagnosis in an angiographically ambiguous focal RAS in FMD. A persistent residual pressure gradient across the lesion despite good angiographic results may be optimized with OCT guidance during the intervention.