This PRISMA-compliant systematic review evaluates the current role of artificial intelligence (AI) in supporting employee physical safety, mental health, and ergonomics in manufacturing, office-based, and healthcare workplaces. Despite rapid technological advances, the majority of existing studies have focused narrowly on technical efficacy while largely neglecting ethical governance, algorithmic bias, data privacy, and alignment with broader business strategy and organizational imperatives. Motivated by these persistent gaps and the urgent need for proactive, personalized, and ethically sound workplace health management, this review synthesizes peer-reviewed evidence on machine learning (ML), natural language processing (NLP), and computer vision applications published between 2019 and 2025. The objectives are threefold: (1) to systematically review the state of research on AI applications in workplace health, (2) to develop and validate a novel integrative framework that connects AI’s technical capabilities with ethical governance and business imperatives, and (3) to identify future challenges and opportunities. This study explicitly aligns its objectives with the three core elements of the title—Technological Integration, Ethical Challenges, and Business Imperatives—by synthesizing evidence on AI applications while addressing ethical governance and organizational strategy. The framework is validated through sector-specific case illustrations in manufacturing (physical safety), office environments (mental well-being), and healthcare (fatigue management). Results show that AI enables proactive interventions that improve health outcomes, yet successful implementation remains limited by data privacy risks, algorithmic bias, lack of transparency, and insufficient attention to organizational culture and employee autonomy. The study’s main contribution is an implementation-ready, equity-focused integrative framework that provides practical guidance for leaders and occupational health professionals aiming to deploy trustworthy AI systems that truly enhance workplace health and organizational well-being.