Multiple sclerosis (MS) pathogenesis is complex, and current clinical treatments cannot halt disease progression and have numerous side effects. There is an urgent need to develop new and effective clinical treatments to improve the clinical symptoms and prognosis of MS patients. Remyelination can provide benefits throughout the entire course of MS, making it a highly promising treatment approach for MS. Oligodendrocyte precursor cells, responsible for myelin regeneration in MS, have their regenerative capacity influenced by various microenvironmental factors. This article provides the first review of the impact and mechanisms of microenvironmental factors such as innate immune cells, myelin debris, extracellular matrix, astrocytes, neurons, pericytes and endothelial cells, adaptive immune cells, peripheral circulation, and aging on MS remyelination, aiming to offer references for the prevention and treatment of MS.