Prostate cancer remains a major global public health concern, with rising incidence rates worldwide, especially in sub-Saharan Africa. Traditional screening modalities, which rely solely on prostate-specific antigen concentration measurement and digital rectal examination (DRE), have shown poor sensitivity and specificity. Hence, this review critically evaluates emerging multimodal diagnostic strategies, including environmental risk assessment, new cytological and immunohistochemical biomarkers, and genomic profiling, to improve early detection and enable precision therapy for prostate cancer. We examine current information on polycyclic aromatic hydrocarbons as environmental risk indicators, the optimization of post-DRE urine cytology, cytological examination of expressed prostate secretions, and the clinical usefulness of biomarkers such as ERBB2, CDK12, BRCA2, and ATM. Specific attention is paid to the African background, where unique genetic and environmental factors necessitate the development of tailored diagnostic algorithms. This integrative approach provides a theoretical framework for developing comprehensive diagnostic pathways that can enhance early detection rates and deliver individualized treatment in resource-constrained environments. Although the target population of this review is sub-Saharan Africans, the principles and frameworks presented have broader applicability to other low- and middle-income nations facing similar challenges.