The University of Oklahoma Health Sciences Center (OU) was awarded a $625,201 Project Grant by the National Cancer Institute (NCI) under the Cancer Cause and Prevention Research (CFDA 93.393) program. The grant will fund a 5-year randomized factorial trial to evaluate the combined impact of varenicline plus nicotine lozenges, with and without a smartphone-based medication adherence intervention, on smoking cessation outcomes among 496 daily cigarette smokers. The primary objectives are to assess 7-day point prevalence abstinence at 26 weeks and medication adherence over the 13-week treatment period. This study aims to improve smoking cessation treatment and reduce cancer risk by exploring the effectiveness of combination pharmacotherapy and a digital adherence intervention. The remote delivery approach utilizing smartphone-based assessments is intended to enhance the study's feasibility and reach.