This systematic review examines the effects of pharmacological adjuncts on transcranial magnetic stimulation (TMS)-induced synaptic plasticity in humans. The review includes studies using repetitive TMS, theta-burst stimulation, paired associative stimulation, and quadripulse stimulation paradigms in healthy and clinical populations. Key findings include: 1. **Pharmacological Agents**: Most studies targeted glutamatergic N-methyl-D-aspartate (NMDA) receptors (15 studies) and dopamine receptors (13 studies). NMDA receptors are necessary for TMS-induced plasticity, but their sufficiency varies across protocols. 2. **Dopaminergic Modulation**: Dopaminergic modulation appears dose-dependent, with low doses enhancing TMS-induced plasticity and high doses reversing it. Studies in clinical populations suggest that pharmacological adjuncts may rescue motor cortex plasticity, with potential therapeutic implications for depression. 3. **Other neurotransmitter systems**: GABAergic, cholinergic, noradrenergic, and serotonergic systems also show small evidence bases supporting modulation of TMS-induced plasticity. 4. **Ion Channels**: Voltage-gated calcium and sodium channels play a role in TMS-induced plasticity, with L-type VGCCs being particularly important for PAS-induced plasticity and T-type VGCCs facilitating LTP- or LTD-like effects. 5. **Clinical Implications**: The review highlights the need for adequately powered samples in healthy and clinical populations to further understand the mechanisms of TMS-induced plasticity and its therapeutic applications. The review concludes that pharmacologically enhanced TMS largely parallels findings from ex vivo preparations, and further research is needed to identify novel targets and optimize parameter selection for therapeutic interventions.This systematic review examines the effects of pharmacological adjuncts on transcranial magnetic stimulation (TMS)-induced synaptic plasticity in humans. The review includes studies using repetitive TMS, theta-burst stimulation, paired associative stimulation, and quadripulse stimulation paradigms in healthy and clinical populations. Key findings include: 1. **Pharmacological Agents**: Most studies targeted glutamatergic N-methyl-D-aspartate (NMDA) receptors (15 studies) and dopamine receptors (13 studies). NMDA receptors are necessary for TMS-induced plasticity, but their sufficiency varies across protocols. 2. **Dopaminergic Modulation**: Dopaminergic modulation appears dose-dependent, with low doses enhancing TMS-induced plasticity and high doses reversing it. Studies in clinical populations suggest that pharmacological adjuncts may rescue motor cortex plasticity, with potential therapeutic implications for depression. 3. **Other neurotransmitter systems**: GABAergic, cholinergic, noradrenergic, and serotonergic systems also show small evidence bases supporting modulation of TMS-induced plasticity. 4. **Ion Channels**: Voltage-gated calcium and sodium channels play a role in TMS-induced plasticity, with L-type VGCCs being particularly important for PAS-induced plasticity and T-type VGCCs facilitating LTP- or LTD-like effects. 5. **Clinical Implications**: The review highlights the need for adequately powered samples in healthy and clinical populations to further understand the mechanisms of TMS-induced plasticity and its therapeutic applications. The review concludes that pharmacologically enhanced TMS largely parallels findings from ex vivo preparations, and further research is needed to identify novel targets and optimize parameter selection for therapeutic interventions.