We examined interactions of overhead work location and direction of force application on shoulder muscular activity. Overhead work tasks are common occupational stressors. Previous research has quantified influences of overhead work spatial placement and different force application directions but typically separately or exclusively for tasks done in the median plane. Twenty female participants exerted 40 N of force in six directions (forward/backward, upward/downward, left/right) 150 cm off the floor while seated. An asymmetric pattern of 14 work locations spaced 15 cm centered directly overhead were evaluated. Force direction and work location strongly influenced mean muscle activity (F = 559, p < .01). Interaction effects existed between force direction and hand location in the transverse plane (F = 21, p < .01), with increases as high as 49% in normalized mean muscle activity. Backward exertions produced the highest mean overall muscle activity across hand force directions, exceeding 30% maximum voluntary isometric exertion (MVE) across work locations, with higher activation of anterior deltoid, biceps, infraspinatus, supraspinatus, and upper and lower trapezius. Downward exertions had the lowest mean overall activity, with <10% MVE across work locations. Altered (up to 47%) muscular activity occurred as exertions moved laterally from the origin, and increasingly forward hand positions generally yielded decreased mean overall activity for most force directions. This study provides previously unavailable submaximal shoulder muscular activity data for a wide range of overhead tasks. As such, it enables novel work design considerations that include modifying existing overhead elements to reduce or redistribute associated muscular demands.