Offshore pile foundations are generally subjected to lateral and vertical loadings. The loss of sand around piles because of scouring reduces the soil resistance and effective depth of pile foundations. Moreover, scour holes are asymmetric both physically and in finite element simulations, which may change the effect of vertical loads on the lateral capacity of pile foundations. In this study, we propose a nonlinear analytical method to estimate the lateral capacity of pile foundations in sand considering vertical loads and asymmetric scour holes. The p–y curve, frictional resistance, shaft resistance moment, and pile-end resistance were revised considering an asymmetric scour hole. The accuracy of the analytical method was validated through comparison with experimental results. The results show that the P–Δ effect caused by vertical loads increases with increasing active scour depth, positive scour depth, active scour width, and positive scour width; and decreasing active and passive scour slopes. The most adverse lateral loading direction was 90° to the water direction with the asymmetric scour hole.