Is it possible to achieve this with a shader

It's definitely possible, and although I've never tried I'm fairly certain this will work.

 Shader "Custom/2 UV Shader" {
     Properties {
         _Color ("Color", Color) = (1,1,1,1)
         _MainTex ("Albedo (RGBA)", 2D) = "white" {}
         _MainTex2 ("Albedo 2 (RGB)", 2D) = "white" {}
         _Glossiness ("Smoothness", Range(0,1)) = 0.5
         _Metallic ("Metallic", Range(0,1)) = 0.0
     }
     SubShader {
         Tags { "RenderType"="Opaque" }
         LOD 200
         
         CGPROGRAM
         // Physically based Standard lighting model, and enable shadows on all light types
         #pragma surface surf Standard fullforwardshadows
 
         // Use shader model 3.0 target, to get nicer looking lighting
         #pragma target 3.0
 
         sampler2D _MainTex;
         sampler2D _MainTex2;
 
         struct Input {
             float2 uv_MainTex;
             float2 uv2_MainTex2;
         };
 
         half _Glossiness;
         half _Metallic;
         fixed4 _Color;
 
         void surf (Input IN, inout SurfaceOutputStandard o) {
             // Albedo comes from a texture tinted by color
             fixed4 c = lerp (tex2D (_MainTex, IN.uv_MainTex), tex2D (_MainTex2, IN.uv2_MainTex2), 1-tex2D (_MainTex, IN.uv_MainTex).a) * _Color;
             o.Albedo = c.rgb;
             // Metallic and smoothness come from slider variables
             o.Metallic = _Metallic;
             o.Smoothness = _Glossiness;
             o.Alpha = c.a;
         }
         ENDCG
     }
     FallBack "Diffuse"
 }
 

This is the normal standard shader, with the alpha value of the first texture blending between the 2 textures.