This study provides an in-depth analysis of the natural characteristics of the Lô River within Phú Thọ Province and elucidates its significance across major economic sectors. It further examines the river’s ecological values and the pressing environmental issues currently confronting the region. On that basis, the paper proposes strategic orientations and comprehensive solutions for the sustainable management, exploitation, and conservation of the Lô River, with the overarching goal of promoting long-term, sustainable development for Phú Thọ Province and the northern midland region as a whole.