Background <p>Few studies investigated factors that predict intensive language therapy (ILT) outcome. This study aimed to analyze multimodal neural factors that possibly underly ILT success.</p> Methods <p>Lesion volume and DTI analyses were performed with 17 aphasic individuals, and complemented by fMRI analysis in 12 patients (due to drop-outs). Structural and functional data were collected at the beginning of a seven&#xa0;week ILT program and correlated with language changes, measured using the Aachen Aphasia Test. Additionally, all analyses were correlated with the patients’ initial aphasia severity.</p> Results <p>Therapy success was associated with functional activity in right inferior and middle temporal gyri, bilateral superior frontal gyrus/ adjacent anterior cingulate cortex, and right occipital lobe (lingual gyrus, fusiform gyrus, lateral occipital cortex). Statistically uncorrected DTI analysis (<i>p</i>(uncorr) &lt; .001) revealed a positive correlation between language improvement and structural integrity in the right temporal lobe and two left-hemisphere white matter clusters (frontal, parietal). Neither global nor language-specific lesion volume was correlated with therapy outcome. However, lesion volume in insula, putamen and white matter tracts was correlated with initial aphasia severity.</p> Conclusions <p>Our preliminary results suggest a predictive role of right temporal structures and functional activation in areas associated with healthy language processing. They also indicate a contribution of functional activation in brain areas associated with cognitive control and non-linguistic semantic processing. Further, lesion volume in both global and language-specific structures proved relevant for the initial severity of aphasia but not for recovery potential following ILT. Our results should be regarded as&#xa0;hypothesis-generating for future research.</p>