OBJECTIVES: To evaluate the effectiveness of the chimeric Free Anterolateral Thigh (FALT) and vastus lateralis muscle (VLM) flap for reconstructing extensive defects in advanced oral squamous cell carcinoma (OSCC), particularly those involving the infratemporal fossa (ITF) and masticator space. METHODS: A retrospective study was conducted at Sri Shankara Cancer Hospital, Bangalore, from January 2023 to June 2024. It included 22 patients with T4a and T4b OSCC who underwent curative ablative surgery, ITF clearance, and reconstruction using the chimeric FALT-VLM flap. The surgical technique involved harvesting a skin paddle based on a single perforator and a separate vastus lateralis muscle from the same donor site. The reconstruction aimed to provide oral cavity lining, oro-cervical separation, and ITF obliteration. RESULTS: Patient age ranged from 38 to 76 years (mean 53.6). The majority had buccal mucosa (54.5%) and retromolar trigone (36.3%) cancers. The FALT skin paddle size varied from 94.2 to 408.2 cm², with muscle bulk between 201.0 and 391.9 cm³. Complications included seroma and hematoma in 9.1% of cases, with 81.8% showing no complications. No donor site morbidity was noted. Post-operative mouth opening ranged between 2.5 and 3.5 cm. Most patients (72.7%) received adjuvant radiotherapy. All maintained local-regional control status. CONCLUSION: The chimeric FALT-VLM flap is a robust technique for reconstructing complex oral cancer defects, effectively addressing both functional and aesthetic needs. This approach, combining skin and muscle components with independent vascular supplies, represents a significant advancement in reconstructive surgery for advanced OSCC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12070-024-05286-3.