Current radiotherapy for malignant tumors often adopts a “one-size-fits-all” approach, prescribing the same irradiation dose for patients with similar clinical indications. However, advancements in functional imaging allow for biologically individualized strategies, with dose distribution tailored to the specific tumor biology. This study proposes a novel approach to biologically individualized radiotherapy, exploiting the synergistic combination of the tumor clonogenic cell information from [¹⁸F]FDG PET images and radiosensitivity from [¹⁸F]fluoromisonidazole (FMISO) PET images. Methods: Twenty-eight patients with head and neck squamous cell carcinoma (HNSCC) were analyzed. Using imaging biomarkers, individualized tumor profiles were obtained from oxygen partial pressure and clonogenic cell density maps derived from [¹⁸F]FMISO and [¹⁸F]FDG PET, respectively. Dose-escalated radiotherapy plans aiming at 95% tumor control probability (TCP) were generated using automated planning. Plans were assessed for clinical feasibility and expected TCP. Results: Planned dose distributions achieved greater than 90% TCP in all cases. All treatment plans met standard clinical feasibility criteria for the main organs-at-risk constraints, except for the few cases with significant target overlap, demonstrating the overall feasibility of the personalized strategy. Conclusion: The proposed biologically individualized treatment strategy demonstrated feasibility and clinical applicability. Combining [¹⁸F]FDG and [¹⁸F]FMISO PET imaging potentially shifts the success rate of HNSCC treatment from approximately 60% at 5 y, as reported in the literature, to a projected TCP of 90%. This treatment strategy holds promise for improving patient outcomes through more precise and effective treatment.