Offshore monopile foundations are exposed to misaligned wind and wave loadings, which are respectively dominated by (nearly) static and cyclic load components. While the response of these systems to unidirectional cyclic loading has been extensively investigated, only a few studies have been devoted to the realistic case of misaligned static and cyclic loads, and particularly to the effects of such misalignment on the accumulation of pile rotation under prolonged cycling. This paper presents a 3D finite-element (FE) modelling study on the relationship between load misalignment and cyclic monopile tilt under drained conditions, based on the use of the SANISAND-MS model to enable accurate simulation of cyclic sand ratcheting. After qualitatively identifying the relationship between relevant loading parameters and cyclic stress/densification mechanisms in the soil, specific parametric studies are performed to explore the impact on pile tilt accumulation. The results show that, in comparison to unidirectional loading, misaligned static–cyclic loading gives rise to lesser-known pile–soil interaction mechanisms: when the direction of cycling deviates from that of the static load, “cyclic compression” and “direct cyclic shearing” mechanisms begin to co-exist. This is quantitatively captured by a newly proposed empirical equation for monopile tilt calibrated against the 3D FE simulation results obtained in this work.