Multi-stage fracturing with horizontal wells is a pivotal technique for developing the unconventional reservoirs. Owing to complex geological conditions coupled with inherent limitations in existing drilling technologies, a significant proportion of horizontal wellbores deviate from the target reservoir, instead inadvertently penetrating adjacent upper and lower interlayers. These misplaced sections are termed the non-reservoir horizontal wellbore intervals (NRHWI). In this scenario, the cross-layer fracturing with directional perforation (CLFDP) is introduced as an effective stimulation method. Despite its potential, the mechanisms governing fracture initiation and propagation in CLFDP operations remain poorly understood. This study, therefore, develops a three-dimensional (3D) numerical model of CLFDP for Well H in the Changqing Oilfield, China. The model specifically considers a horizontal wellbore positioned within the mudstone interlayer overlying the target sandstone reservoir and incorporates realistic perforation geometry. We systematically investigate fracture morphological characteristics, injection pressure dynamics, and fracture area evolution. The goal is to examine how these parameters are influenced by variations in wellbore location, perforation depth, and perforation spacing. The results demonstrate that a distinctive gourd-shaped fracture yields in the CLFDP case. The horizontal wellbore trajectory should be optimally steered to maximize reservoir contact, leveraging advanced technologies such as rotary steering systems—a critical factor in enhancing stimulation efficiency. In scenarios where the horizontal wellbore deviates from the target reservoir, we recommend employing deep-penetration perforation (with large perforation depth) combined with high-density perforation (reduced perforation spacing) to effectively develop the NRHWI. These outcomes provide essential theoretical underpinnings and technical support to maximally harness the unconventional resources.