Introduction: Complex epilepsy networks with multifocal onset zones that overlap with eloquent cortex may benefit from combined surgical approaches. However, limited data exist on outcomes associated with performing these therapies in tandem. In this case series, we report on 6 patients who underwent combination surgery with either resection or laser interstitial thermal therapy (LITT) and neuromodulation with responsive neurostimulation (RNS) or deep brain stimulation (DBS). Methods: We performed a retrospective review of adult patients with medically refractory epilepsy who underwent staged combination epilepsy surgeries during the same admission at our institution. Six cases treated between 2019 and 2023 were identified. All patients underwent a presurgical work-up including invasive intracranial monitoring and underwent a combined approach with either surgical resection, LITT, RNS, or DBS. We extracted data on demographic, clinical, and surgical characteristics. The primary outcome was change in seizure frequency from baseline. Results: The mean age was 42.7 years old (4 female). All patients had at least one epileptogenic zone in the temporal lobe, two in extratemporal neocortex, two in periventricular nodular heterotopia. For the staged combination approach, 3 patients underwent LITT followed by RNS, two underwent resection and RNS, and one received LITT and DBS. The mean reduction in seizure frequency per month at last follow-up was 90%. Postoperatively, 1 patient experienced superior visual field deficits related to LITT, and another had postoperative deep vein thrombosis. Conclusion: All patients experienced at least an 83% reduction in seizures. This case series demonstrates the potential benefits of a combined surgical approach in patients with multifocal seizures and at least one lesion that can be safely resected or ablated. Future prospective studies are warranted.