This thesis work highlights development and applications for both circulating extracellular vesicles (EV) and cell-free RNA (cf-RNA) toward liquid biopsy based early cancer detection methodologies. Effective detection and monitoring for signatures of oncological disease in a noninvasive manner are urgently needed to reduce the morbidity and mortality caused by cancer. Circulating EVs and cf-RNA are intensely sought after biomarkers in liquid biopsy. Their roles in cell-to-cell communication, ability to reflect phenotypic changes from cells, and tissues of origin are becoming better understood. Despite this, current literatures present key challenges which limit the promise of liquid biopsy based early cancer detection: i) there is a lack of standardized blood processing for multi-omics which minimizes ex-vivo processing artefacts via discerning true in-vivo signatures from ex-vivo artefacts; ii) daily fluctuations and the influence of meal consumption on EV and cf-RNA levels are not clear; iii) a comprehensive study of cf-RNA for cancer detection, pan cancer discernment, and high risk group identification has not been conducted; and iv) the selective packaging of cf-RNA carriers and its association with cancer are unknown.