Prostate cancer is the second most commonly diagnosed cancer in men worldwide. This thesis leverages novel single-cell epigenomic and proteomic approaches to aid in the identification of precise subtypes of prostate tumors that are organ-confined at the time of diagnosis. We first utilize cyclic immunofluorescent imaging to profile the spatial heterogeneity of prostate tumors and uncover risk-level and Gleason Pattern specific cell types and cellular interactions. Next, we perform single-cell ATAC sequencing of the same tumors and identify unique genomic regions associated with high-risk tumors and immune response signatures associated with low-risk tumors. Finally, we develop assays that enable multiplex imaging of biomarkers isolated from low-volume liquid biopsy samples. Our work uncovers unique cellular and molecular markers, which hold the potential to become novel prognostic factors, and presents a multiplex liquid biopsy approach for the detection of prostate cancer for precise treatment strategies.