Post-traumatic stress disorder (PTSD) is characterized by persistent traumatic memories and flashbacks, which may arise from dysregulated synaptic plasticity mediated by inflammatory and epigenetic mechanisms. Three intervention strategies are evaluated in this paper. They are exercise and exposure therapy, targeted drugs, and personalized repetitive transcranial magnetic stimulation (rTMS) respectively. Inflammatory and epigenetic pathways are integrated in this framework to provide a new perspective on PTSD synaptic pathology mechanism. Restoring the balance between long-term potentiation (LTP) and long-term depression (LTD) should be an important therapeutic target. Future studies should validate LTP and LTD changes in patients and develop personalized combination therapies based on plasticity subtypes. Studies have found that traumatic stress can promote excessive enhancement of the amygdala's LTP through abnormal activation of the hypothalamic–pituitary–adrenal (HPA) axis, leading to reinforced fear memories. Simultaneously, it can inhibit hippocampal LTD processes through Brain-derived neurotrophic factor (BDNF) DNA methylation and related signaling alterations, thus hindering the extinction of traumatic memories. The NF-κB inflammatory pathway and the BDNF methylation pathway may serve as key molecular nodes which regulate synaptic plasticity imbalance. Based on these mechanisms, this article further summarizes intervention strategies for restoring synaptic plasticity balance, including exercise combined with exposure therapy, targeted drug therapy, and personalized rTMS therapy.