The impact of Xylella fastidiosa (Xf) subsp. pauca on the environment and economy of Southern Italy has been devastating. To restore the landscape and support the local economy, introducing new crops is crucial for restoring destroyed olive groves, and the almond tree (Prunus dulcis Mill. D. A. Webb) could be a promising candidate. This work focused on the resistance of the cultivar "Filippo Ceo" to Xf and evaluated its physiological and molecular responses to individual stresses (drought or pathogen stress) and combined stress factors under field conditions over three seasons. Filippo Ceo showed a low pathogen concentration (≈103 CFU mL-1) and a lack of almond leaf scorch symptoms. Physiologically, an excellent plant water status was observed (RWC 82-89%) regardless of the stress conditions, which was associated with an increased proline content compared to that of the control plants, particularly in response to Xf stress (≈8-fold). The plant's response did not lead to a gene modulation that was specific to different stress factors but seemed more indistinct: upregulation of the LEA and DHN gene transcripts by Xf was observed, while the PR transcript was upregulated by drought stress. In addition, the genes encoding the transcription factors (TFs) were differentially induced by stress conditions. Filippo Ceo could be an excellent cultivar for coexistence with Xf subps. pauca, confirming its resistance to both water stress and the pathogen, although this similar health status was achieved differently due to transcriptional reprogramming that results in the modulation of genes directly or indirectly involved in defence strategies.