Background <p>Informal caregivers, frequently family members or close acquaintances, offer uncompensated care and support to individuals with cardiovascular diseases, confronting diverse challenges such as mental stress, financial strain, and the overall burden of care. Addressing these challenges is vital for both caregivers and patients. This systematic review seeks to identify the factors contributing to caregiver burden among informal caregivers of cardiovascular patients.</p> Methods <p>PubMed, Scopus, ProQuest, Web of Science, and Science Direct were searched from 2000 until July 2023, following the PRISMA guidelines, to systematically retrieve relevant papers. The review incorporated quantitative, qualitative, and mixed-methods studies.</p> Results <p>Forty-two studies were included in the systematic review. Data synthesis adhered to the Joanna Briggs Institute (JBI) methodological guidance using a convergent integrated approach. Five categories emerged: individual characteristics (demographic characteristics of the caregiver and patient-related factors), confronting multifaceted tensions (physical problems, mental health problems, and financial burden), role strain in daily life, inadequate health literacy, and lack of support.</p> Conclusion <p>This review underscores that informal caregivers of cardiac patients encounter substantial burdens. These burdens are intensified by challenges, including insufficient knowledge, restricted social support, and suboptimal communication from both family members and healthcare providers, resulting in increased physical and psychological stress. It is crucial to evaluate informal caregivers for these burdens and offer the required support. Clinical implications include routine assessment of caregiver burden, providing tailored educational interventions to enhance health literacy, and offering financial and psychosocial support to mitigate risks specific to cardiovascular disease caregiving.</p>