The effect of treatment by zoledronic acid combined with exemestane was explored pertaining to the immune function, sex hormones, bone markers, and clinical efficacy in hormone receptor-positive breast cancer patients. Eighty elderly patients with hormone receptor-positive breast cancer were selected as the study subjects who were clinically admitted from December 2016 to December 2021. The study and control groups had 40 cases each and were analyzed according to different treatment methods. The control group received exemestane treatment, while the study group was treated with a combination of zoledronic acid and exemestane. The immune functions, sex hormones, bone markers, clinical efficacy, adverse reactions, life quality scores, serum calcium, and vascular endothelial growth factor for the two groups were analyzed and compared. The cluster of differentiation (CD), E2, P and T levels were lower than those of the control after treatment, and the difference was statistically significant, p < 0.05. Similar effect was observed in β-Cross Laps, serum calcium levels and N-terminal propeptide of type 1precollagen (PINP) levels. Physiological and psychological scores were higher than the control after treatment, and difference was statistically significant, p < 0.05. The incidence of adverse reactions was 20.00% for the study group while 42.50% for control, and the difference was statistically significant, p < 0.05. We conclude that Zoledronic acid combined with exemestane in treating hormone receptor-positive breast cancer patients could improve clinical efficacy, immune function, bone metabolism, quality of life, regulate the sex hormones, and possess drug safety.