A method for execution by one or more processing modules to configure a programmable drive-sense unit (DSU) includes determining one or more load sensing objectives based on sensing a load using the DSU that is configured to drive and simultaneously to sense the load via a single line. The method further includes determining one or more data processing objectives associated with sensing the load. The method further includes determining desired characteristics for the output data associated with sensing the load. The method further includes determining operational parameters for the DSU based on one or more of the load sensing objectives, the data processing objectives, and the desired characteristics for the output data. The method further includes configuring the DSU based on the operational parameters to achieve the one or more load sensing objectives.