Objective To assess the fatigue status and its related influencing factors in patients after thyroid cancer surgery, and to alleviate postoperative fatigue and improve their quality of life through precision nursing interventions. Methods A total of 400 patients who underwent thyroid cancer surgery in our hospital from November 2019 to October 2021 were enrolled and randomly divided into an experimental group and a control group (200 patients in each group). The experimental group received precision nursing interventions including anxiety management, progressive neck and shoulder functional exercises, thyroid function follow-up, nutritional adjustment, and sleep improvement after surgery, while the control group received routine postoperative care. The fatigue status was assessed using the Improved Chronic Fatigue Syndrome Scale (ICFS-10), the shoulder and neck function was evaluated using the Constant-Murley Shoulder Score System, and anxiety, sleep, pharyngeal discomfort, and quality of life were assessed using the Hospital Anxiety and Depression Scale (HADS), Pittsburgh Sleep Quality Index (PSQI), Visual Analogue Scale (VAS), and Short Form-36 Health Survey (SF-36). The results of these assessments were analyzed on postoperative day 1, day 3, 1 month, and 3 months. Results The fatigue scores in the experimental group were significantly lower than those in the control group at 1 month and 3 months after surgery; the shoulder and neck function scores in the experimental group were significantly higher than those in the control group at 3 months after surgery. The HADS and PSQI scores in the experimental group were significantly lower than those in the control group at 3 months after surgery (all P<0.05). Conclusion Precision nursing interventions significantly improved the fatigue status, anxiety levels, and sleep quality of patients after thyroid cancer surgery, demonstrating their effectiveness in postoperative rehabilitation. It is recommended for clinical application.