Abstract Motivation Large-scale population omics data can provide insight into associations between gene–environment interactions and disease. However, existing dimension reduction modelling techniques are often inefficient for extracting detailed information from these complex datasets. Results Here, we present an interactive software pipeline for exploratory analyses of population-based nuclear magnetic resonance spectral data using a COmbined Multi-block Principal components Analysis with Statistical Spectroscopy (COMPASS) within the R-library hastaLaVista framework. Principal component analysis models are generated for a sequential series of spectral regions (blocks) to provide more granular detail defining sub-populations within the dataset. Molecular identification of key differentiating signals is subsequently achieved by implementing Statistical TOtal Correlation SpectroscopY on the full spectral data to define feature patterns. Finally, the distributions of cross-correlation of the reference patterns across the spectral dataset are used to provide population statistics for identifying underlying features arising from drug intake, latent diseases and diet. The COMPASS method thus provides an efficient semi-automated approach for screening population datasets. Availability and implementation Source code is available at https://github.com/cheminfo/COMPASS. Supplementary information Supplementary data are available at Bioinformatics online.