The prediction of drug-target interactions (DTIs) is a vital step in drug discovery. The success of machine learning and deep learning methods in accurately predicting DTIs plays a huge role in drug discovery. However, when dealing with learning algorithms, the datasets used are usually highly dimensional and extremely imbalanced. To solve this issue, the dataset must be resampled accordingly. In this paper, we have compared several data resampling techniques to overcome class imbalance in machine learning methods as well as to study the effectiveness of deep learning methods in overcoming class imbalance in DTI prediction in terms of binary classification using ten (10) cancer-related activity classes from BindingDB. It is found that the use of Random Undersampling (RUS) in predicting DTIs severely affects the performance of a model, especially when the dataset is highly imbalanced, thus, rendering RUS unreliable. It is also found that SVM-SMOTE can be used as a go-to resampling method when paired with the Random Forest and Gaussian Naïve Bayes classifiers, whereby a high F1 score is recorded for all activity classes that are severely and moderately imbalanced. Additionally, the deep learning method called Multilayer Perceptron recorded high F1 scores for all activity classes even when no resampling method was applied.