This chapter outlines a flexible connectome-based predictive modeling method that is optimised for large neuroimaging datasets via the use of parallel computing and by adding the capability to account for possible site- and scanner-related heterogeneity in multi-site neuroimaging datasets. We present the decision points that need to be made when conducting a connectome-based predictive modeling analysis and we provide full code to conduct an analysis on public data. To date, connectome-based predictive modeling has been applied to predict different cognitive and behavioural phenotypes with many studies reporting accurate predictions that generalized to external datasets.