Background: Accurately predicting the risk of diabetic foot ulceration (DFU) could dramatically reduce the enormous burden of chronic wound management and amputation. Yet, the current prognostic models are unable to precisely predict DFU events. Typically, efforts have focused on individual factors like temperature, pressure, or shear rather than the overall foot microclimate. Methods: A systematic review was conducted by searching PubMed reports with no restrictions on start date covering the literature published until February 20, 2019 using relevant keywords, including temperature, pressure, shear, and relative humidity. We review the use of these variables as predictors of DFU, highlighting gaps in our current understanding and suggesting which specific features should be combined to develop a real-time microclimate prognostic model. Results: The current prognostic models rely either solely on contralateral temperature, pressure, or shear measurement; these parameters, however, rarely reach 50% specificity in relation to DFU. There is also considerable variation in methodological investigation, anatomical sensor configuration, and resting time prior to temperature measurements (5-20 minutes). Few studies have considered relative humidity and mean skin resistance. Conclusion: Very limited evidence supports the use of single clinical parameters in predicting the risk of DFU. We suggest that the microclimate as a whole should be considered to predict DFU more effectively and suggest nine specific features which appear to be implicated for further investigation. Technology supports real-time in-shoe data collection and wireless transmission, providing a potentially rich source of data to better predict the risk of DFU.