This document outlines a precision conservation initiative across the Mississippi River Basin to address issues impacting wildlife, water quality, and agriculture from the prairies to the Gulf of Mexico. It proposes integrating the efforts of various agencies and organizations using spatial analysis and targeted practices. The initiative would identify 12 high-impact conservation practices and focus on 6 Midwest watersheds. It would develop pilot projects in the Lower Wabash Floodplain and Decatur County, Indiana to test the approach at smaller scales. Applied research on human dimensions and integrated performance metrics is also proposed. The overall goal is to leverage conservation efforts across sectors for multiple benefits.