The pathogenesis of SARS-CoV-2 infection involves intricate molecular pathways, with notable implications for host physiology and disease progression. Two key pathways, the Renin–Angiotensin system (RAS) and the Kallikrein-Kinin system (KKS), are central to understanding the pathophysiology of COVID-19. SARS-CoV-2 utilizes the angiotensin-converting enzyme 2 (ACE2) receptor for cell entry, influencing RAS dynamics and contributing to the dysregulation of blood pressure and inflammation. Similarly, activation of the KKS pathway, mediated by mast cells, exacerbates vascular permeability and inflammatory responses in severe COVID-19 cases. Furthermore, dysregulated immune responses, characterized by cytokine storms and aberrant signaling pathways, play pivotal roles in disease severity and multiorgan dysfunction. The interleukin-6 (IL-6) pathway, Toll-like receptor (TLR) signaling, and interferon-gamma (IFN-γ) responses are implicated in the dysregulated immune milieu observed in severe COVID-19. Additionally, signal transduction pathways such as PI3K/Akt/mTOR, NF-κB, MAPK, and HIF-1 pathways are intricately involved in orchestrating host responses to viral infection, highlighting potential therapeutic targets. Targeting these pathways holds promise for mitigating inflammation, viral replication, and tissue damage associated with SARS-CoV-2 infection. This comprehensive understanding of molecular pathways in SARS-CoV-2 infection is critical for effective therapeutic interventions and management strategies to combat COVID-19 disease.