Lupus, a chronic autoimmune disease affecting multiple organ systems, encompasses a broad range of clinical manifestations. Systemic lupus erythematosus (SLE), the most prevalent form of lupus, presents with considerable heterogeneity, posing substantial challenges in disease management for patients, providers, and caregivers. Despite overall improvements in SLE outcomes, disparities persist across various population subgroups due to environmental and personal factors, and lead to SLE deterioration and suboptimal outcomes. Recognizing the critical role of addressing these environmental and personal risks in SLE management, we integrate real-world data (RWD), artificial intelligence (AI), and natural language processing (NLP) to tackle data and methods challenges and propose to develop an individualized risk management tool that aims to build holistic care for SLE, facilitating a much-needed paradigm shift in US health care delivery. This SBIR project is an interdisciplinary collaboration among Polygon Health Analytics LLC and the University of Florida. By leveraging RWD from the OneFlorida+ network and an exposome database capturing environmental and personal risk factors, we aim to (1) establish an individualized risk score, which assesses increased environmental and personal risks essential to SLE flares, and (2) employ causal AI models to estimate the causal effect of environmental and personal risk factors on SLE flares to identify the effective targets for interventions. (Aim 1) Moreover, collaborating with various stakeholders, our team will prototype a digital health tool named iSMILE (Individualized Social Risk Management In Systematic Lupus Erythematosus CarE) through a user-centered design (UCD) approach and develop thoughtful qualitative studies to develop next-step implementation recommendations and commercialization plans. (Aim 2) This project is highly feasible and potentially transformative for creating novel holistic care for SLE patients. It will deliver the prototype of iSMILE tailored for individual SLE patients with input from various stakeholders along with a set of prioritized strategies for implementation. We will also refine a step-by-step commercialization plan to identify a viable business model, targeting various stakeholders (e.g., patients, payers, and pharma companies), in order to further develop the ISMILE into a real commercial tool with a bigger scope through a SBIR Phase II project.