Chronic inflammation is a pivotal driver in the progression of atherosclerosis, significantly contributing to the burden of cardiovascular disease (CVD). Patients with chronic inflammatory diseases, such as inflammatory bowel diseases (IBDs) (e.g., ulcerative colitis and Crohn's disease), rheumatological disorders, as well as individuals with auto-immune diseases (such as systemic lupus erythematosus), present a higher risk of major adverse cardiac events (MACEs). Despite their elevated CVD risk, these populations remain underrepresented in cardiovascular research, leading to a critical underestimation of their cardiovascular risk (CVR) in clinical practice. Furthermore, even recent CVR scores poorly predict the risk of events in these specific populations. This narrative review examines the physiopathological mechanisms linking chronic inflammation, immunomodulation, atherosclerosis, thrombosis and cardiovascular events. We review data from epidemiological studies and clinical trials to explore the potential cardiovascular benefits of anti-inflammatory and immunomodulatory therapies. Despite existing evidence, significant gaps in knowledge remain. Future research is mandatory, focusing on innovative strategies for risk stratification and optimization, including lipidomics, proteomics, advanced inflammatory markers, microbiota profiling, and cardiovascular imaging. Addressing these unmet needs will enhance understanding of cardiovascular risk in chronic inflammatory diseases, enabling tailored interventions and better outcomes.