Purpose <p>This study aimed to investigate the effects of different intensities of resistance exercise on shoulder function and immune response in young and middle-aged breast cancer patients after surgery.</p> Methods <p>A total of 114 patients who underwent modified radical mastectomy for breast cancer at Tangshan People’s Hospital from July 2023 to July 2024 were randomly assigned to three groups: the control group (routine nursing), intervention group 1 (routine care + low-intensity resistance exercise), and intervention group 2 (routine care + moderate-to-high intensity resistance exercise). Shoulder function was assessed using the Constant-Murley Score (CMS), and immune markers (perforin, granzyme B, and perforin/granzyme B activity) were evaluated at baseline, post-intervention, and at a 3-month follow-up.</p> Results <p>Prior to intervention, no significant differences in shoulder function or immune markers were observed across the groups (<i>P</i> &gt; 0.05). Post-intervention and at the 3-month follow-up, intervention group 2 showed significant improvements in joint mobility, pain, muscle strength, total CMS scores, and immune markers compared to both the control and intervention group 1 (<i>P</i> &lt; 0.001). Intervention group 1 demonstrated improvements in immune markers only at the 3-month follow-up compared to the control group (<i>P</i> &lt; 0.001).</p> Conclusion <p>Resistance exercise is an effective rehabilitation strategy for improving shoulder function and immune response in young and middle-aged breast cancer patients after surgery. Moderate-to-high intensity resistance exercise yields superior benefits and should be considered in clinical rehabilitation protocols.</p>