In recent years, the treatment of drug-resistant epilepsy (DRE) has made greater use of surgery and expanded options for neurostimulation or neuromodulation. Up to this point, responsive neurostimulation (RNS) has been very promising but has mainly used only the cortex as a target. In this individual patient data meta-analysis (IPDMA), the authors sought to establish if a novel RNS target, the thalamus, can be used to treat DRE. The literature regarding the management of DRE by targeting the thalamus with RNS was reviewed per IPDMA guidelines. Five databases were searched with keywords [((Responsive neurostimulation) OR (RNS)) AND ((thalamus) OR (thalamic) OR (Deep-seated) OR (Diencephalon) OR (limbic))] in March 2022. The median (interquartile range) age at implantation was 17 (13.5-27.5) years (n = 42) with an epilepsy duration of 12.1 (5.8-15.3) years. In total, 52.4% of patients had previously undergone epilepsy surgery, 28.6% had prior vagus nerve stimulation, and 2.4% had prior RNS. The median preimplant seizure frequency was 12 per week. The median seizure reduction at last follow-up was 73%. No study in this IPDMA reported complications, although 7 cases (16.3%) did require reoperation. Behavioral improvements and reduced antiepileptic drug dose or quantity were reported for 80% and 28.6% of patients, respectively. This review indicates that thalamic RNS may be safe and effective for treating DRE. Long-term and controlled studies on thalamic RNS for DRE would further elucidate this technique's potential benefits and complications and help guide clinical judgment in the management of DRE.