•Stroke represents the leading cause of disability in the industrialized world.•Post-stroke impairment interferes with the QoL of the patient and caregiver.•Robot-assisted hand training allow to perform practical tasks with a VR setting.•Hand robotic plus VR-based training may amplify the functional outcome achievement. Robot-assisted hand training adopting end-effector devices results in an additional reduction of motor impairment in comparison to usual care alone in different stages of stroke recovery. These devices often allow the patient to perform practical, attentive, and visual-spatial tasks in a semi-virtual reality (VR) setting. We aimed to investigate whether the hand end-effector robotic device AmadeoTM could improve cognitive performance, beyond the motor deficit, as compared to the same amount of occupational treatment focused on the hand. Forty-eight patients (aged 54.3 ± 10.5 years, 62.5% female) affected by either ischemic or hemorrhagic stroke in the chronic phase were enrolled in the study. The experimental group (EG) underwent AmadeoTM robotic training, while the control group (CG) performed occupational therapy involving the upper limb. Patients were assessed at the beginning and at the end of the rehabilitation protocol using a specific neuropsychological battery, as well as motor function tests. The EG showed greater improvements in different cognitive domains, including attentive abilities and executive functions, as well as in hand motor function, as compared to CG. Our study showed that task-oriented VR-based robotic rehabilitation enhanced not only motor function in the paretic arm but also global and specific cognitive abilities in post-stroke patients. We may argue that the hand robotic plus VR-based training may provide patients with an integration of cognitive and motor skill rehabilitation, thus amplifying the functional outcome achievement.