Socioeconomic status (SES)-related health disparities are worsening substantially in the U.S. and elsewhere, including Canada, Australia, New Zealand, Japan, Korea, Hong Kong, and even egalitarian Nordic European countries with robust social safety nets (Denmark, Norway, Sweden, and Finland). Preventable mortality is difficult to mitigate for a multitude of reasons, including numerous determinants at individual, interpersonal, community, and societal levels. However, there is some cause for optimism based on the potency of action levers at the individual level. Among SES- and race/ethnicity-related health disparities in the U.S., 11 preventable conditions cause >50% of mortality. Further, our preliminary modeling work suggests that only 9 prevention goals are required to attain 40% mortality reduction from these 11 conditions, resulting in 20% mortality reduction overall, because of interdependencies and common pathways. For example, alcohol use disorder and/or heavy drinking impacts not only liver failure, but also behavioral consequences such as sexual risk-taking and medication nonadherence. However, attaining 20% mortality reduction would require a radical transformation of preventive care, such as what we propose, focused on personalization, navigation, and compensation. Personalization means maximizing individual-level benefit by modulating intensity of screening, frequency of screening; and intensity or duration of response; navigation means reducing barriers posed by fragmentation of health and social systems; and compensation means offsetting dependent care, time costs, and travel costs. The post-R34-goal is a N=15,000 5-year RCT which would have adequate power to test the hypothesis of 20% mortality reduction from personalization, navigation, and compensation. This proposed R34 is preparatory for that goal, and focuses especially on alcohol use disorder and heavy drinking, HIV risk, and risk for cardiovascular disease.