The advancement in cancer research using high throughput technology and artificial intelligence (AI) is gaining momentum to improve disease diagnosis and targeted therapy. However, the complex and imbalanced data with high dimensionality pose significant challenges for computational approaches and multi-omics data analysis. This study focuses on predicting skin cancer and analyzing overall survival probability. We employ the Kaplan–Meier estimator and Cox proportional hazards regression model, utilizing high-throughput machine learning (ML)-based ensemble methods. Our proposed ML-based ensemble techniques are applied to a publicly available dataset from the ICGC Data Portal, specifically targeting skin cutaneous melanoma cancers (SKCM). We used eight baseline classifiers, namely, random forest (RF), decision tree (DT), gradient boosting (GB), AdaBoost, Gaussian naïve Bayes (GNB), extra tree (ET), logistic regression (LR), and light gradient boosting machine (Light GBM or LGBM). The study evaluated the performance of the proposed ensemble methods and survival analysis on SKCM. The proposed methods demonstrated promising results, outperforming other algorithms and models in terms of accuracy compared to traditional methods. Specifically, the RF classifier exhibited outstanding precision results. Additionally, four different ensemble methods (stacking, bagging, boosting, and voting) were created and trained to achieve optimal results. The performance was evaluated and interpreted using accuracy, precision, recall, F1 score, confusion matrix, and ROC curves, where the voting method achieved a promising accuracy of 99%. On the other hand, the RF classifier achieved an outstanding accuracy of 99%, which exhibits the best performance. We compared our proposed study with the existing state-of-the-art techniques and found significant improvements in several key aspects. Our approach not only demonstrated superior performance in terms of accuracy but also showcased remarkable efficiency. Thus, this research work contributes to diagnosing SKCM with high accuracy.