BACKGROUND: Previous research has typically focussed on the neuromodulatory effects of direct currents applied over single regions of the cortex. However, complex processes such as working memory (WM) strongly rely on activations across a wider neural network and therefore might benefit from stimulation administered over multiple cortical targets. OBJECTIVE: We examined the neurobiological and cognitive effects of High-Definition transcranial direct current stimulation (HD-tDCS) montages that either targeted the dorsolateral prefrontal cortex (DLPFC) alone, or simultaneously stimulated the DLPFC and parietal cortex (DLPFC + PC). METHODS: In a within-subjects design, 16 healthy participants completed three experimental sessions in which they received HD-tDCS over either the DLPFC, the DLPFC + PC or sham stimulation. Changes in cortical reactivity were examined using transcranial magnetic stimulation combined with electroencephalography (TMS-EEG), while oscillatory power was measured via EEG recorded during n-back tasks. WM performance was also examined across several separate tasks. RESULTS: Stimulation using both the DLPFC or DLPFC + PC montages modulated cortical reactivity, as indexed by potentiation of the P60 TMS-evoked potential. However, only the dual-site DLPFC + PC stimulation produced a reduction in the amplitude of the N100 component, relative to baseline. Increases in theta and gamma power were also observed following this montage, when compared to baseline, but were not present following HD-tDCS over the DLPFC alone. Despite these neurophysiological changes, WM performance was not significantly modulated by HD-tDCS, regardless of stimulation montage. CONCLUSION: These results provide important initial insight into the behavioural and biological effects of stimulation over key cortical regions linked to WM and attest to the sensitivity of TMS-EEG and EEG in detecting subtle neurophysiological changes induced by HD-tDCS.