The objective of this study is to understand relations between multiple physical and environmental factors and red tide, which is a common name for harmful algal blooms occurring along coastal regions worldwide. Large concentrations of Karenia brevis, a toxic mixotrophic dinoflagellate, make up the red tide along the West Florida Shelf (WFS) in the Gulf of Mexico. Besides being toxic, red tide causes unpleasant odor and scenery, which result in multiple environmental and socioeconomic impacts and public health issues. Understanding the physical and biogeochemical processes that control the occurrence of red tide is important for studying the impact of climate change on red tide frequency, and accordingly assessing the future environmental and socioeconomic impacts of red tide under different mitigation techniques and climate scenarios. We use observation and reanalysis data in the WFS to train machine learning (ML) models to predict red tide, as a classification problem of large bloom or no bloom. We develop the ML model using seasonal input data of Peace River and Caloosahatchee River outflow, alongshore and offshore wind speed, and Loop Current position. The Loop Current, which is a warm ocean current that enters and loops through the Gulf of Mexico before exiting to join the Gulf Stream, can be detected from sea surface height. In addition to the observation and reanalysis data, these variables can be simulated by the Earth system models (ESMs) of the Coupled Model Intercomparison Project Phase 6 (CMIP6), especially by the high-resolution models of the High Resolution Model Intercomparison Project (HighResMIP) of CMIP6. This is needed to understand the frequency and future trends of red tide under different Shared Socioeconomic Pathways (SSPs) of CMIP6. In this preliminary study, we investigate the impact of different choices regarding ML model selection and training dataset on the accuracy of red tide prediction, and the physical interpretation of the results. We also discuss the validation of ESMs data for predictive modeling, and ensemble methods for improving predictive performance. The study provides several insights that can be useful for predicting the future trends of red tide under SSPs using CMIP6 data.