Background/Objectives: Multiple underlying pathomechanisms may lead to melasma, but there has been no report on the use of optical coherence tomography (OCT) to reveal specific pathomechanisms in individual patients and provide individualized treatments accordingly. Using real-time OCT images, we studied the pathomechanisms of melasma in 12 female patients and the effects of individualized treatments. Methods: Patients were divided into good and bad improved groups according to the improvement in hyperpigmentation at month 4. Results: In the bad improved group, all melanin or confetti melanin had significantly decreased at month 2 or month 4 while granular melanin ratio at month or month 4 significantly increased, the most parameters of dendritic-sharped cells (DCs) before and after treatment were not significantly different, the collagen area or collagen density at month 4 significantly decreased. In the good improved group, there was slightly low all melanin/confetti melanin at month 4 and high granular melanin at month 4 in comparison to the bad improved group. Moreover, most of the parameters in the DCs at month 4 significantly increased while most parameters in collagen at month 4 significantly decreased. Conclusions: OCT is useful in revealing the involved pathomechanisms of melasma in individualized patients. Positive treatment results can be achieved through individualized therapy regimen targeting the pathomechanisms.