Background: To define the impact of psychological support intervention within cardiovascular rehabilitation in a "real world" context by assessing health-related quality of life, perceived levels of anxiety and depression, and changes in these parameters before and after the rehabilitation program. Materials and Methods: A retrospective analytical study was conducted. Clinical records of 102 patients from February 2022 to December 2023 undergoing cardiovascular rehabilitation at the Noale Hospital (Veneto, Italy) were analyzed. The cohort primarily included patients with recent STEMI, outcomes of cardiac surgery, chronic ischemic heart disease and cardiomyopathies. The program lasted 12 weeks and included aerobic, strength, and flexibility training, mostly at moderate intensity. At the same time, patients underwent psychological support sessions, and health-related quality of life, anxiety, and depression levels were assessed using questionnaires (SF-36, Zung SAS and Zung SDS) at the beginning and at the end of the program. Results: A significant increase (p<0.001) in the scores of the administered questionnaires was observed from the start to the end of the program in the study population, as well as in the analyzed subgroups (men [p<0.001], women [p<0.05], acute conditions [p<0.001], chronic conditions [p<0.05], surgical patients [p<0.05], non-surgical patients [p<0.001], patients with normal/slightly reduced VO2max [p<0.001], and patients with moderately/severely reduced VO2max [p<0.001]). When comparing different subgroups (men vs. women, acute vs. chronic conditions, etc.), the impact of the intervention appeared comparable across most of the analyzed domains. Conclusions: Exercise-based cardiovascular rehabilitation program combined with psychological support intervention in a "real world" context has shown to be effective in improving perceived health-related quality of life, anxiety, and depression levels in the study population.