Mood disorders, including depression, remain a significant global health concern, necessitating continuous efforts to develop novel and more effective antidepressant therapies. Although there have been significant advancements in comprehending the biology of Major Depressive Disorder (MDD), a considerable number of people suffering from depression do not exhibit positive responses to the pharmacologic treatments now available. This study specifically examines emerging targets and potential future approaches for pharmaceutical interventions in the treatment of MDD. The discussion revolves around novel therapeutic agents and their effectiveness in treating depression. The focus is on the specific pathophysiological pathways targeted by these agents and the amount of evidence supporting their use. While conventional antidepressants are anticipated to continue being the primary treatment for MDD in the foreseeable future, there is currently extensive research being conducted on numerous new compounds to determine their effectiveness in treating MDD. Many of these compounds have shown encouraging results. This review highlighted the recent advances in the synthesis of antidepressant derivatives and explores their pharmacologic insights for the treatment of mood disorders.