After the death of Padre Pio, the Saint’s friars thought of constructing a new church, because too sensitive to the material and spiritual needs of the devotees, that the existing church could not contain. After the presentation of several projects, Friars entrusted the design of a new church to the architect Renzo Piano, so that it could accommodate 6,500 people. For its size it is the second largest church in Italy, after St. Peter's Church in Rome.

Long dedicated to Santa Maria delle Grazie, the new Sanctuary conceived by Renzo Piano occupies – with its enormous conch-shell structure - and represents the second-largest church in Italy after Milan's Duomo. Finally opened after ten years of construction, and also known as the Church of St. Pio, the new Sanctuary was almost entirely financed by the offerings of pilgrims. Today it can hold up to 6,500 people at once.

San Michele Pilgrimage Shrine consists of the original Sanctuary of the Archangel Michael in a grotto and the crypt and devotional museums. It's easy to find the shrine as the octagonal bell tower, built in the 13th century, rises above the town of Monte Sant' Angelo on Puglia's Gargano Promontory. From the small square by the bell tower, pilgrims and tourists pass through the Gothic arches of San Michele. Descending the long stone staircase constructed in the 13th century (or elevator for the disabled), visitors arrive in the nave with frescoes and murals. On the Bronze doors, made in 1076 in Constantinople, are 24 panels depicting Bible scenes. The doors lead to the cave of Saint Michael. The Sanctuary of the Archangel Michael, or San Michele, in the grotto dates from the 5th - 6th centuries and is the site where devotion to the Archangel Michael began. The original grotto of San Michele is said to have been consecrated by the archangel and is the only church not consecrated by human hands.

The Shrine is on the ancient Via Sacra Langobardorum, connecting important Longobard sites, now a UNESCO World Heritage Site. It's also a major stop on the Pilgrimage route for devotees of the Archangel Michael that connects Mont St Michelin.