The rapid growth of e-business in the digital transformation era has brought significant cybersecurity challenges. This study aims to analyze holistic defense strategies to comprehensively protect e-business assets and operations. Utilizing a systematic literature review of 50 reputable scientific publications (2020–2024), the study identifies five key pillars of cybersecurity strategy: (1) multi-layered security architecture, (2) AI-powered threat detection, (3) Zero Trust security model, (4) continuous security monitoring, and (5) human-centric security culture. The integrated implementation of these pillars has been shown to reduce cybersecurity risks by up to 78% and accelerate threat detection by 89%. These findings highlight the importance of integrating advanced technologies, mature processes, and strong security awareness to establish a resilient cybersecurity ecosystem for e-business.