Cellular automata (CA) and artificial neural networks (ANNs) have been used by researchers over the last three decades to simulate land-use change (LUC). While conventional CA and ANN models assign a cell to only one land-use class, in reality, a cell may belong to several land-use classes simultaneously. The recently developed multi-label (ML) concept overcomes this limitation in land change science. Although the ML concept is a new paradigm with nonexclusive classes and has shown considerable merit in several applications, few studies in land change science have applied it. In addition, determining transition rules in conventional CA is difficult when the number of drivers is large. Since CA has been shown as a potential model to consider neighborhood effects and ANN has been shown effective in determining CA transition rules, we integrated both CA with an ANN model to overcome limitations of each tool. In this study, we specifically extended the ANN-based Land Transformation Model (LTM) with both a CA-based model and the ML concept to create an integrated ML-CA-LTM modeling framework. We also compared, using standard evaluation measures, differences between the proposed integrated model with a conventional CA-based LTM model (called the ml-CA-LTM). Parameterization was made using a learning and testing procedure common in machine learning. Results showed that the modified LUC model, ML-CA-LTM, produced consistently better goodness of fit calibration values compared to the ml-CA-LTM. The outcome of this modified model can be used by managers and decision makers for improved urban planning.