Background: Oncology patients frequently get multiple medications, including herbal supplements and medicines (chemotherapy, supportive care, comorbidities drugs, self-medication). This might pose a serious risk for drug interactions (DI) and non-drug interactions (NDI), which could endanger the patient's health. Our aims are to characterize the interactions, describe the risks to the patient they pose, and suggest a course of action to be followed. Methods: To make a pharmaceutical validation of chemotherapy prescriptions, this prospective study—the first of its kind at the national level—was carried out at the level of the Medical Oncology Department of CHU-Tlemcen from November 2021 to February 2022. It included patients treated on an outpatient basis who were receiving chemotherapy and/or targeted therapy. Following a medication reconciliation interview, patients from our sample who are being treated for one or more comorbidities are chosen in order to detect DIs using two French platforms (Vidal, Theriaque) and one Anglo-Saxon platform (Drugs). Hedrine was utilized to detect NDIs. Results: A total of 76 patients were enrolled for chemotherapy pharmaceutical validation. 36 (47%) of them were interviewed (median age = 61 years [42-86], sex ratio = 0,2), had at least one comorbidity treatment and 16 patients (45%) had breast cancer. The most frequently used protocols were anthracyclines (10 patients; 28%), anthracycline-taxanes (5 patients; 14%), capecitabine (5 patients; 14%), and capecitabine-oxaliplatin (3 patients; 8%). Seven patients (19%) used herbal supplements, primarily black seed (Nigella sativa L.). Forty different interactions were listed for Vidal (23 precautions for use, 18 to be considered), 4 involved a chemotherapy drug. Forty-seven interactions with Theriaque (7 new interactions that Vidal missed, including 5 undesirable associations due to the use of ethanol as an excipient with a notable effect), 8 were due to a chemotherapy drug. On Drugs, 102 interactions were observed (4 serious, 90 moderated, and 8 minor), 38 involved a chemotherapeutic agent. Most interactions necessitated clinical and/or biological patient monitoring. In terms of NDIs, Hedrine indicates possible interactions by cross-referencing the effects of different plants on the organism with those of drugs, without giving any indication of the level of risk, what to do in case of risk. This makes interpretation difficult and requires expert opinion to guide action. No serious events were reported in the study. Conclusions: It is worthwhile to continue the pharmaceutical interview, especially for those most at risk for drug interactions, i.e., the elderly and/or patients on multiple medications. To widen the scope of interaction detection, it should be carried out prior to the recommendation of chemotherapy and refreshed when a patient's protocol changes utilizing at least one French and one Anglo-Saxon database.