This work is part of a larger set of conversations on how philanthropic capital can better deliver potent results. This paper is intended for philanthropists and foundation staff who are interested in understanding not only which issues and interventions might put many more low-income people on an upward trajectory, but also how private donors can use their dollars, networks, and voices to achieve systemic change. Based on their review of the research on social mobility, the authors identified four sprawling opportunities for philanthropic investors to help ensure that far more Americans have a chance to reach their full potential. Using the frame of a philanthropist investing $1 billion, the authors have constructed a set of 15 big bets across each of the four general investment areas. The bets consider specifically how a philanthropist could support efforts to improve outcomes for low-income populations across race, gender, and geographic differences. For donors seeking to give big to catalyze greater levels of social mobility and build sustainable pathways out of poverty for low-income Americans, this paper aims to: (1) provide a draft frame of "what matters most" to help an individual attain social mobility (or be "middle class by middle age"); (2) highlight ways that philanthropists can use a broad set of tools--beyond funding nonprofits--to support enduring impact; (3) develop an illustrative set of 15 investment opportunities ("bets") that map out how to spend $1 billion to drive change at scale; and (4) provide preliminary estimates of the potential return on investment for six of the $1 billion bets. [For the Executive Summary, see ED606513. For the Overview of Research, see ED606515. For the Overview of Estimated Returns on Six Big Investments and Their Impacts on Lifetime Earnings, see ED606518.]