BACKGROUND Soft-tissue reconstruction of the scalp has traditionally been challenging in oncologic patients. Invasive tumors can compromise the calvarium, necessitating alloplastic cranioplasty. Titanium mesh is the most common alloplastic material, but concerns of compromise of soft-tissue coverage have introduced hesitancy in utilization. The authors aim to identify prognostic factors associated with free-flap failure in the context of underlying titanium mesh in scalp oncology patients. METHODS A retrospective review (2010-2018) was conducted at a single center examining all patients following oncologic scalp resection who underwent titanium mesh cranioplasty with free-flap reconstruction following surgical excision. Patient demographics, comorbidities, ancillary oncological treatment information were collected. Operative data including flap type, post-operative complications including partial and complete flap failure were collected. RESULTS A total of 16 patients with 18 concomitant mesh cranioplasty and free-flap reconstructions were identified. The majority of patients were male (68.8%), with an average age of 70.5 years. Free-flap reconstruction included 15 ALT flaps (83.3%), 2 latissimus flaps (11.1%), and one radial forearm flap (5.5%). There were three total flap losses in two patients. Patient demographics and comorbidities were not significant prognostic factors. Additionally, post-operative radiation therapy, ancillary chemotherapy, oncological histology, tumor recurrence, and flap type were not found to be significant. Pre-operative radiotherapy was significantly associated with flap failure (P < 0.05). CONCLUSIONS Pre-operative radiotherapy may pose a significant risk for free-flap failure in oncologic patients undergoing scalp reconstruction following mesh cranioplasty. Awareness of associated risk factors ensures better pre-operative counseling and success of these reconstructive modalities and timing of pre-adjuvant treatment.