The transition from Industry 4.0 to Industry 5.0 marks a shift from purely technological optimisation to a value-driven paradigm that emphasises human-centeredness, sustainability, and resilience. Despite the widespread adoption of artificial intelligence (AI) in industrial operations, existing implementations often focus predominantly on operational efficiency, neglecting the cognitive load, psychological well-being, and decision-making capacities of human operators. To address this critical gap, this study proposes a multi-layered Socio-Technical Framework for AI-Driven Cognitive Ergonomics, designed to integrate human-centred design principles with intelligent automation systematically. Building upon advancements in Human Digital Twins (HDTs), neurophysiological sensing (EEG and eye-tracking), wearable health devices (smartwatches, biosensing patches, smart rings, and EEG-enabled headbands), and collaborative robotics, the framework integrates both real-time physiological data streams and operators’ historical health records stored in enterprise databases to deliver personalised cognitive support. Organised into two interconnected tiers — the Human-Centric Tier and the Organisational-Management Tier — the framework demonstrates how AI can harmonise individual cognitive support, human-cobot collaboration, and management-level decision-making through adaptive interfaces, real-time feedback mechanisms, and dynamic task allocation strategies. A conceptual application in a collaborative assembly scenario illustrates the framework’s practical relevance, highlighting how Operator 5.0 maintains situational awareness, control, and trust through explainable AI (XAI) and shared mental models. Simulation and analytical evaluations indicate that integrating cognitive ergonomics with AI-assisted systems enhances productivity, reduces operator workload, and improves team coordination. By aligning AI capabilities with human factors, the proposed framework delivers actionable guidance for designing socially sustainable, human-centred smart factories. These findings underscore that the successful realisation of Industry 5.0 depends not solely on automation but also on the deliberate harmonisation of AI with human cognitive and ergonomic needs, ensuring that industrial workplaces remain resilient, adaptive, and fundamentally people-centred.