Exercise training is a well-known non-pharmacological strategy for the prevention and treatment of cardiovascular diseases. Despite the established phenotypic knowledge, the molecular signature of exercise-induced cardiac remodeling remains poorly characterized. The great majority of studies dedicated to this topic use conventional reductionist methods, which only allow analyzing individual protein candidates. Nowadays, several methodologies based on mass spectrometry are available and have been successfully applied for the characterization of heart proteome, representing an attractive approach for the wide characterization of the complex molecular networks that underlie exercise-induced cardiac remodeling. Still, few studies have used these methodologies to understand the impact of exercise training on the remodeling of cardiac proteome. The present study analyzes the few available data obtained from mass spectrometry (MS)-based proteomic studies assessing the impact of distinct types of exercise training on the protein profile of heart (left ventricle and isolated mitochondria) and the potential cross-tolerance between exercise training and diseases as myocardial infarction and obesity. Network analysis was performed with bioinformatics to integrate data from distinct research papers, based on distinct exercise training protocols, animal models and methodological approaches applied in the characterization of heart proteome. The analysis revealed that exercise training confers a unique proteome signature characterized by the up-regulation of lipid and organic metabolic processes, vasculogenesis and tissue regeneration. Data retrieved from this analysis also suggested that cardiac mitochondrial proteome is highly dynamic in response to exercise training due, in part, to the action of specific kinases as PKA and PKG. Regarding to the type of exercise, treadmill training seems to have a greater effect on the modulation of cardiac proteome than swimming. Data from the present review will certainly open new perspectives on cardiac proteomics and will help to envisage future studies targeting the identification of the regulatory mechanisms underlying cardiac adaptive and maladaptive remodeling.