MRONJ (Medication-Related Osteonecrosis of the Jaw) is a condition observed in a subset of cancer patients who have undergone treatment with zoledronic acid in order to either prevent or treat bone metastases. The primary aim of this research was to establish the importance of risk factors in the development of medication-related osteonecrosis of the jaw in cancer patients receiving zoledronic acid therapy for bone metastases. The present study is an observational retrospective investigation conducted at two university centers, namely, Craiova and Constanța, and included cancer patients treated with zoledronic acid. The medical records of the patients were obtained over a four-year timeframe spanning from June 2018 to June 2022. The data analysis was carried out between January 2021 and October 2022. Patients were treated for cancer, bone metastases, and MRONJ according to the international guidelines. The research investigated a cohort of 174 cancer patients (109 females and 65 males) aged between 22 and 84 years (with a mean age 64.65 ± 10.72 years) seeking treatment at oncology clinics situated in Craiova and Constanța. The study conducted a binomial logistic regression to analyze ten predictor variables, namely, gender, age, smoking status, treatment duration, chemotherapy, radiotherapy, endocrine therapy, presence of diabetes mellitus (DM), obesity, and hypertension (HT). The results of the analysis revealed that only five of the ten predictor variables were statistically significant for MRONJ occurrence: duration of treatment ( < 0.005), chemotherapy ( = 0.007), and hypertension ( = 0.002) as risk factors, and endocrine therapy ( = 0.001) and obesity ( = 0.024) as protective factors.