Personalized treatment of complex diseases relies on combined medication. However, the occurrence of unexpected drug–drug interactions (DDIs) in these combinations can lead to adverse effects or even fatalities. Although recent computational methods exhibit promising performance in DDI screening, their practical implementation faces two significant challenges: (i) the availability of comprehensive datasets to support clinical application, and (ii) the ability to infer DDI types for new drugs beyond the existing dataset coverage. To mitigate these challenges, we propose MM-GANN-DDI: a Multimodal Graph-Agnostic Neural Network for Predicting Drug–Drug Interaction Events. We first mine six drug modalities and incorporate a graph attention (GAT) mechanism to fuse these modalities with the topological features of the DDI graph. We further propose a novel graph neural network training mechanism called graph-agnostic meta-training (GAMT), which effectively leverages topological information from the DDI graph and efficiently predicts DDI types for new drugs beyond the available dataset. Specifically, GAMT samples meta-graphs from the original DDI graph, splitting them into support and query sets to simulate seen and unseen drugs. Two-level optimizations are applied to enhance the model’s generalization capability.We evaluate our model on two datasets (DB-v1 and DB-v2) across three tasks. Our MM-GANN-DDI demonstrates competitive performance on all three tasks. Notably, in Task 2, which focuses on predicting DDI types for drugs outside the dataset, our proposed model outperforms other methods, exhibiting an improvement of 4.6 percentage points in AUPR on DB-v1 and 5.9 percentage points on DB-v2. Additionally, our model surpasses state-of-the-art methods and classic approaches in terms of accuracy, F1 score, precision, and recall. Ablation experiments provide further validation of the effectiveness of the proposed model design. Importantly, our model exhibits the potential to discover unobserved DDIs, demonstrating its practical application in clinical medication.