Complex, distributed, and dynamic sets of clinical biomedical data are collectively referred to as multimodal clinical data. In order to accommodate the volume and heterogeneity of such diverse data types and aid in their interpretation when they are combined with a multi-scale predictive model, machine learning is a useful tool that can be wielded to deconstruct biological complexity and extract relevant outputs. Additionally, genome-scale metabolic models (GSMMs) are one of the main frameworks striving to bridge the gap between genotype and phenotype by incorporating prior biological knowledge into mechanistic models. Consequently, the utilization of GSMMs as a foundation for the integration of multi-omic data originating from different domains is a valuable pursuit towards refining predictions. In this chapter, we show how cancer multi-omic data can be analyzed via multimodal machine learning and metabolic modeling. Firstly, we focus on the merits of adopting an integrative systems biology led approach to biomedical data mining. Following this, we propose how constraint-based metabolic models can provide a stable yet adaptable foundation for the integration of multimodal data with machine learning. Finally, we provide a step-by-step tutorial for the combination of machine learning and GSMMs, which includes: (i) tissue-specific constraint-based modeling; (ii) survival analysis using time-to-event prediction for cancer; and (iii) classification and regression approaches for multimodal machine learning. The code associated with the tutorial can be found at https://github.com/Angione-Lab/Tutorials_Combining_ML_and_GSMM.